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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.

This study aims to explore the mechanism of Shoutai Pills in treating threatened abortion. According to the random number table method, ICR female mice were randomized into a normal group, a model group, a dydrogesterone group, and a Shoutai Pills group, with 15 mice in each group. Mice were administrated with normal saline(normal and model groups) or the suspension of Shoutai Pills or dydrogesterone by gavage at 9:00 am every day. At 16:00 every day, mice in the normal group were administrated with an equal volume of distilled water, while those in the model, Shoutai Pills, and dydrogesterone groups were administrated with hydrocortisone solution by gavage for 4 consecutive days. ICR female and male mice were caged in a ratio of 2∶1 during the pre-estrous or estrous period. From the first day of pregnancy, drug administration was continued for 5 consecutive days. On day 6, mice were administrated with mifepristone by gavage to establish the model of kidney deficiency-induced abortion. On day 6 of pregnancy, 10 female ICR mice were randomly selected from each group, and the uterus was collected for observation of the pathological changes of trophoblasts at the maternal-fetal interface by hematoxylin-eosin(HE) staining. The protein levels of key enzymes of glycolysis, hexokinase 2(HK2), enolase 1(ENO1), pyruvate kinase M2(PKM2), and lactate dehydrogenase A(LDHA), were determined by Western blot and immunofluorescence. The expression of apoptosis-related proteins including B cell lymphoma-2(Bcl-2), Bcl-2-associated protein X(Bax), and cysteinyl aspartate-specific proteinase-3(caspase-3) was determined by Western blot and real-time PCR. Terminal-deoxynucleoitidyl transferase-mediated nick-end labeling was employed to examine apoptosis. The embryo loss rate of the remaining five female mice was calculated by trypan blue staining method on day 14 of pregnancy. On day 14 of pregnancy, the embryo loss rate of the normal group was 5.00%, which was lower than that(27.78%) in the model group(P<0.05). Dydrogesterone and Shoutai Pills groups showed reduced embryo loss rates(10.26% and 7.50%, respectively) compared with the model group. On day 6 of pregnancy, compared with the normal group, the model group showed down-regulated expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and up-regulated expression of Bax and caspase-3(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills up-regulated the expression of HK2, ENO1, PKM2, LDHA, and Bcl-2 and down-regulated the expression of Bax and caspase-3(P<0.05). Compared with that in the normal group, the apoptosis rate in the model group increased(P<0.05). Compared with the model group, dydrogesterone and Shoutai Pills reduced the apoptosis rate(P<0.05). In conclusion, Shoutai Pills can reduce the embryo loss rate and protect embryos by promoting aerobic glycolysis at the maternal-fetal interface and inhibiting the apoptosis of trophoblasts in mice.

Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients., Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed., Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects., Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario., Competing Interests: Conflicts to interest: none to declare., (© 2024. Federação Brasileira de Ginecologia e Obstetrícia. All rights reserved.)

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., Competing Interests: Declaration of Competing Interest The authors have declared that they have no conflicts of interests in connection with this article, (Copyright © 2023 Elsevier Masson SAS. All rights reserved.)

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., Competing Interests: Declaration of interest We confirm that this work is original and has not been published elsewhere, nor is it currently under consideration for publication elsewhere. We have no conflicts of interest to disclose., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., (Copyright © 2022. Published by Elsevier Inc.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

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 (E 2 ) 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., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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., Competing Interests: The authors declare no competing interests., (Copyright © 2022 Xuehong Chen et al.)

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 (β-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 β-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 β-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 β-hCG MoM values compared to pregnancies without vaginal bleeding during pregnancy.

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., (© 2021 International Federation of Gynecology and Obstetrics.)

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)., Competing Interests: The authors have declaredthat no competing interests exist.

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.

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 STATEMENT What 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.

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., (Copyright © 2021. Published by Elsevier Ltd.)

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 20⁰⸍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.

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 Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

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., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

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.

Progesterone is essential for the maintenance of pregnancy, and progesterone deficiency is associated with miscarriage. The subject of whether progesterone supplementation in early pregnancy can prevent miscarriage has been a long-standing research question and has been investigated and debated in the medical literature for over 70 years. During this time, several different progestogens have been synthesised and tested for the prevention of miscarriage. In this chapter, we describe the prior evidence alongside the latest research using micronized natural progesterone as well as synthetic progestogens, which were used to treat both recurrent and threatened miscarriage. The totality of evidence indicates that women with a past history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone. The clinical implications of the findings are discussed., Competing Interests: Declaration of competing interest There are no conflicts of interest to report., (Copyright © 2020. Published by Elsevier Ltd.)

This observational study examines the outcomes of pregnancies arising in women referred for infertility, where those who experienced threatened miscarriage were treated with medroxyprogesterone acetate (MPA) tablets. The 14-year study period covers comprehensive real-time data entries into the validated electronic database including details of the infertility management, pregnancy outcomes and any foetal anomalies among the infants, each being tracked and recorded. Of 4057 clinical pregnancies, 1343 received MPA for threatened miscarriage; 934 (69.6 %) of which continued to livebirths. These were compared with the remaining 2714 clinical pregnancies without threatened miscarriage or MPA and which resulted in 2075 (76.5 %) livebirths. There were 134 developmental abnormalities recorded among the 3009 livebirths of which 78 (2.6 %) were categorised appropriate for the Western Australian Developmental Abnormalities Register; WARDA. These comprised 55 in the MPA group, 36 of which were categorised as serious (being 2.7 % of clinical pregnancies and 3.9 % of births). In the group without MPA, there were 79 abnormalities, of which 42 were categorised as serious (being 1.7 % of clinical pregnancies and 2.2 % of births). Specifically, there were no cases of androgenisation noted among the female infants. The abnormality rates were low overall and well within the annual WARDA ranges. We cautiously suggest that oral MPA can be considered for studies throughout pregnancy including the early first trimester to assess a potential role in reducing miscarriage, as well as advanced pregnancies to evaluate a potential role in reducing stillbirths and preterm delivery., Competing Interests: Declaration of Competing Interest The project was funded internally under an existing long-term collaboration between PIVET Medical Centre and Curtin University, which supports a Fellowship position for KNK. JLY is Medical Director of PIVET and adjunct Clinical Professor at Curtin University. The corresponding author JLY can confirm that none of the authors have any conflicts of interest to declare., (Copyright © 2020 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. Published by Elsevier B.V. All rights reserved.)

Background: Threatened miscarriage is a common complication of pregnancy. Results of randomised controlled trials on the efficacy of progestogen in the treatment of threatened miscarriage remain inconsistent., Objective: To investigate whether the use of progestogen is associated with improved event rate of live birth and other benefits in women with threatened miscarriage., Search Strategy: Ovid MEDLINE, Ovid Embase and Cochrane CENTRAL Register of Controlled Trials from their inception until 8 July 2019., Selection Criteria: Randomised controlled trials comparing progestogen with a placebo or no treatment for pregnancy outcomes in women with threatened miscarriage., Data Collection and Analysis: Two authors independently conducted data extraction and assessed study quality. We calculated risk ratios (RR) and 95% confidence intervals using the Mantel-Haenszel approach for dichotomous outcomes., Main Results: Ten trials with a total of 5056 participants were eligible for analysis. The use of progesterone increased the incidence of live birth (RR 1.07, 95% CI 1.00-1.15; P = 0.04; I 2  = 18%), with benefit only seen with the use of oral progestogen (RR 1.17, 95% CI 1.04-1.31; P = 0.008; I 2  = 0%) and not with vaginal progesterone (RR 1.04, 95% CI 1.00-1.08; P = 0.07; I 2  = 0%). Similarly, progestogen reduced the risk of miscarriage (RR 0.73, 95% CI 0.59-0.92), with benefit only seen with oral progestogen and not with vaginal progesterone., Conclusion: Progestogens may have benefits on live birth rate and miscarriage rate for women with threatened miscarriage. These benefits appear to be confined to the use of oral progestogen, and no statistically significant improvements were seen with vaginal progesterone., Tweetable Abstract: A meta-analysis of 10 trials found that progestogens increased live birth rates and reduced miscarriage rates for women with threatened miscarriage., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making., (Copyright © 2019 The Author(s). Published by Elsevier Inc. All rights reserved.)

Threatened abortion (TA) is a common complication with high incidence in the first trimester of pregnancy, which will end in miscarriage if not treated properly. The Chinese herbs Cuscutae Semen (Tusizi in Chinese) and Herba Taxilli (Sangjisheng in Chinese) first recorded in the ancient classic medical book Shennong Bencao Jing are effective and widely used as an herb pair for the treatment of TA, while the active ingredients and the functional mechanism of Tusizi-Sangjisheng herb pair treating TA are still unknown. In order to exploit the relationship between those two herbs and TA, systems pharmacology analysis was carried out in this study. A total of 75 ingredients of Tusizi-Sangjisheng were collected from Traditional Chinese Medicine System Pharmacology Database and Analysis Platform (TCMSP). 12 bioactive compounds were screened, and 153 directly related targets were predicted by systematic models. Besides, Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were used to systematically explore the potential mechanisms of Tusizi-Sangjisheng treating TA. Meanwhile, Compound-Target (C-T), Target-Disease (T-D), and Target-Pathway (T-P) networks were constructed to further quest the underlying functional mechanisms of Tusizi-Sangjisheng. As a result, 31 targets and 3 key pathways were found to be directly related to TA that includes mitogen-activated protein kinases (MAPKs), phosphatidylinositol-3-kinase/protein kinase B (PI3K-Akt), and transforming growth factor- β (TGF- β ) signaling pathways. The results in this study may provide some valuable clues about the molecular mechanisms of the efficient Chinese herb pair Tusizi-Sangjisheng in the treatment of TA., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2020 Ming Yang et al.)

Background: To compare the clinical efficacy and safety of phloroglucinol (PHL) and magnesium sulfate (MS) in the treatment of threatened abortion through systematic review., Methods: Foreign databases, such as the Cochrane Library, PubMed and EMBASE, and Chinese databases, including the China Biology Medicine disc (SinoMed), China National Knowledge Infrastructure (CNKI), Chongqing VIP (VIP) and WanFang Data, were searched. Published randomized controlled trials (RCTs) documents obtained from these databases were included if they were associated with the research objective. The search timeframe was from the beginning of the establishment of each database to May 2018. Document selection, data abstraction and document quality evaluation were independently performed by 2 investigators. A combined analysis of the data was performed for those documents that fulfilled the study requirements; Rev Man 5.3 and Stata 12.0 software were used to compare and analyze the 2 drugs in terms of the total effective rate (TER), rate of adverse events, time required to relieve uterine contractions, onset time, time of complete relief of uterine contraction symptoms, medication duration and length of hospital stay., Results: A total of 21 RCT trials were included in the present research, according to the inclusion criteria. However, the quality of the included studies was low. The meta-analysis suggested that the TER and drug onset time of PHL were higher than those for MS, while the rate of adverse events, the time required to relieve uterine contractions, time to complete relief of uterine contraction symptoms, drug continuous treatment time and length of hospital stay were shorter than those for MS., Conclusion: The clinical efficacy of PHL is better than that of MS, and PHL obviously results in fewer adverse reactions than MS. However, due to poor quality of evidence, high quality, multi-center RCTs with large samples are required for further verification.

Objective To examine the association between maternal diseases and congenital heart defects (CHDs) and to evaluate whether those associations vary with corresponding medication use. Methods A multi-hospital case-control study conducted from February 2010 to December 2014 analysed 916 controls and 1236 cases. Participating mothers were asked whether they suffered from influenza, common cold, herpes and threatened abortion or had used corresponding medication during the periconception period or the early pregnancy period. We used a random-effects logistic regression model to compute the odds ratios (ORs), adjusted odds ratios (AORs) and 95% confidence intervals (CIs) while controlling for potential confounders. Results Compared with the results for mothers with no exposure, there were significant associations between maternal diseases with medication non-use and CHDs in the aggregate, including influenza (AOR, 1.83; 95% CI, 1.13-2.95), common cold (AOR, 2.05; 95% CI, 1.60-2.64) and herpes (AOR, 7.00; 95% CI, 2.15-22.84). There was no significant association between medication users and offspring with any subtype of CHDs, except that maternal common cold with medication use slightly increased the risk of the specific subtype, namely, isolated cardiac defects. However, an association was observed between maternal threatened abortion and medication and isolated cardiac defects (AOR, 1.33; 95% CI, 1.01-1.75). Conclusion Maternal influenza, common cold, herpes and threatened abortion from 3 months before pregnancy through the first trimester were associated with an increased risk of congenital heart disease in offspring. The teratogenic effect of these conditions may be attenuated by medication use, except for threatened abortion.

Aim: To investigate whether treatment with progesterone would decrease the incidence of miscarriage in women who faced threatened miscarriage., Methods: Randomized controlled trials (RCT) were identified by searching PubMed, Embase, Cochrane Library and Web of Science. Trials were included if they compared progesterone with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage. Pregnant prophylaxis drugs were not included without strict progesterone type, language and progesterone management. The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI)., Results: Eight RCT including 845 women who faced threatened miscarriage were analyzed. Pooled data from the eight trials showed that women with threatened miscarriage who were randomized to the progesterone group had a lower risk of threatened miscarriage (RR = 0.64, 95% CI 0.48-0.85). Dydrogesterone was shown to have a lower risk of miscarriage (RR = 0.49, 95% CI 0.33-0.75) than natural progesterone (RR = 0.69, 95% CI 0.40-1.19). Oral management was demonstrated to have a lower risk of miscarriage (RR = 0.55, 95% CI 0.38-0.79) compared with vaginal administration (RR = 0.58, 95% CI 0.28-1.21)., Conclusion: Our findings show that progesterone agents are effective in reducing the incidence of miscarriage in threatened miscarriage. Dydrogesterone, but not natural progesterone, was associated with a lower risk of miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progesterone therapy. Further head-to-head trials of gestational weeks and long-time follow-up are required., (© 2019 Japan Society of Obstetrics and Gynecology.)

Threatened abortion is a common complication of pregnancy. Since the underlying mechanisms behind this condition are complicated, predicting and treating threatened abortion is a challenge for clinicians. Interestingly, a recent article in Bioscience Trends (Biosci Trends 2019; DOI: 10.5582/bst.2019.01111) revealed a higher, not lower, level of ꞵ-human chorionic gonadotropin (hCG) and estrogen during the first 6 weeks of pregnancy, suggesting a novel association between ꞵ-hCG, estrogen, and threatened abortion. Unfortunately, this study was limited by its small sample size, unconvincing trial design, and inadequate exploration of the underlying mechanisms. This low-quality evidence indicates that a higher level of ꞵ- hCG and estrogen is associated with threatened abortion. However, that work provided some new insights for further studies of threatened abortion.

There has not been conclusive evidence in literature on the efficacy of progestogen in the treatment of threatened miscarriage, although some studies showed benefits. In our centre, threatened miscarriage is treated with either micronised progesterone (MP) or dydrogesterone (DYD)., Objective: The aim of this study is to compare clinical outcomes of miscarriage, extent of vaginal bleeding at follow-up and side effects between treatment groups., Study Design: This study was a prospective parallel-group, open-label, randomized controlled trial. 141 women presenting with threatened miscarriage were randomised to either MP or DYD of which 118 were included in the analysis. Baseline maternal demographics and serum progesterone levels were collected at presentation. Post-treatment bleeding pattern and self-reported side effects were recorded at the follow-up visit (on day 4-10 of treatment). The occurrence of spontaneous miscarriage was ascertained at week 16 of gestation., Results: The population with miscarriage and resolution of bleeding were not statistically different between MP and DYD groups. A significantly higher percentage of women treated with MP reported drowsiness (p = 0.003). After stratification into low and high serum progesterone levels, a significantly higher miscarriage rate was found in the low progesterone group, regardless of treatment type., Conclusion: In conclusion, extent of bleeding at day 4-10 and subsequent miscarriage rates were comparable between MP and DYD groups. However, fewer patients treated with DYD reported drowsiness and giddiness. The finding of significantly higher miscarriage rates in women with low progesterone levels despite treatment is an important factor to consider in counselling and prognosticating pregnancy outcomes., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Miscarriage is a common complication encountered during pregnancy. It is defined as spontaneous pregnancy loss before 20 weeks' gestation. Progesterone's physiological role is to prepare the uterus for the implantation of the embryo, enhance uterine quiescence and suppress uterine contractions, hence, it may play a role in preventing rejection of the embryo. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss. This update of the Cochrane Review first published in 2007, and previously updated in 2011, investigates the evidence base for this practice., Objectives: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage., Search Methods: We searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (8 August 2017) and reference lists of retrieved trials., Selection Criteria: Randomised, quasi-randomised or cluster-randomised controlled trials, that compared progestogen with placebo, no treatment or any other treatment for the treatment of threatened miscarriage in women carrying singleton pregnancy., Data Collection and Analysis: At least two review authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data and graded the body of evidence., Main Results: We included seven trials (involving 696 participants) in this update of the review. The included trials were conducted in different countries, covering the full spectrum of the World Bank's economic classification, which enhances the applicability of evidence drawn from this review. Two trials were conducted in Germany and Italy which are high-income countries, while four trials were conducted in upper-middle income countries; two in Iran, one in Malaysia and the fourth in Turkey, and the seventh trial was conducted in Jordan, which is a lower-middle income country. In six trials all the participants met the inclusion criteria and in the seventh study, we included in the meta-analysis only the subgroup of participants who met the inclusion criteria. We assessed the body of evidence for the main outcomes using the GRADE tool and the quality of the evidence ranged from very low to moderate. Downgrading of evidence was based on the high risk of bias in six of the seven included trials and a small number of events and wide confidence intervals for some outcomes.Treatment of miscarriage with progestogens compared to placebo or no treatment probably reduces the risk of miscarriage; (risk ratio (RR) 0.64, 95% confidence interval (CI) 0.47 to 0.87; 7 trials; 696 women; moderate-quality evidence). Treatment with oral progestogen compared to no treatment also probably reduces the miscarriage rate (RR 0.57, 95% CI 0.38 to 0.85; 3 trials; 408 women; moderate-quality evidence). However treatment with vaginal progesterone compared to placebo, probably has little or no effect in reducing the miscarriage rate (RR 0.75, 95% CI 0.47 to 1.21; 4 trials; 288 women; moderate-quality evidence). The subgroup interaction test indicated no difference according to route of administration between the oral and vaginal subgroups of progesterone.Treatment of preterm birth with the use of progestogens compared to placebo or no treatment may have little or no effect in reducing the rate of preterm birth (RR 0.86, 95% CI 0.52 to 1.44; 5 trials; 588 women; low-quality evidence).We are uncertain if treatment of threatened miscarriage with progestogens compared to placebo or no treatment has any effect on the rate of congenital abnormalities because the quality of the evidence is very low (RR 0.70, 95% CI 0.10 to 4.82; 2 trials; 337 infants; very-low quality evidence)., Authors' Conclusions: The results of this Cochrane Review suggest that progestogens are probably effective in the treatment of threatened miscarriage but may have little or no effect in the rate of preterm birth. The evidence on congenital abnormalities is uncertain, because the quality of the evidence for this outcome was based on only two small trials with very few events and was found to be of very low quality.

Purpose: To compare the effect of oral micronized progesterone (OMP) on the first-trimester fetal and placental volumes using three-dimensional ultrasonography and extended imaging virtual organ computer-aided analysis (XI VOCAL) method in threatened abortion., Methods: This randomized controlled trial enrolled women with threatened abortion and a singleton pregnancy from 6-8 6/7 weeks of gestation. A total of 60 women with threatened abortion were randomly assigned to one of two groups: OMP (400 mg/day) (n = 30) and control groups (n = 30). The XI VOCAL method was used for all volume measurements using three-dimensional ultrasonography. All patients were evaluated for fetal, amniotic, and placental volumes during the initial diagnosis and after 4 weeks., Results: After treatment, placental volume difference was significantly higher in the OMP group (336%, 67-1,077) than in the control group (141%, 29-900) (p = 0.007). The mean differences in gestational sac, amniotic sac, and embryonic volumes between the OMP and control groups were not statistically significant., Conclusions: Hormonal support with OMP is associated with increased placental volume in first-trimester threatened abortion when compared with the control group. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:14-19, 2017., (© 2016 Wiley Periodicals, Inc.)

Objective: To conduct systematic analyses to evaluate the efficacy of progesterone therapy for the prevention of miscarriages in pregnant women experiencing threatened abortion., Methods: In November 2016, we performed a systematic literature search and identified 51 articles in PubMed, Embase, and Cochrane databases. We identified nine randomized trials that included 913 pregnant women (including 322 treated with oral dydrogesterone, 213 treated with vaginal progesterone, and 378 control subjects) who met the selection criteria., Results: The incidence of miscarriage was significantly lower in the total progesterone group than in the control group (13.0% versus 21.7%; odds ratio, 0.53; 95% confidence interval (CI), 0.36 to 0.78; P = 0.001; I 2 , 0%). Moreover, the incidence of miscarriage was significantly lower in the oral dydrogesterone group than in the control group (11.7% versus 22.6%; odds ratio, 0.43; 95% CI, 0.26 to 0.71; P = 0.001; I 2 , 0%) and was lower in the vaginal progesterone group than in the control group, although this difference was nonsignificant (15.4% versus 20.3%; odds ratio, 0.72; 95% CI, 0.39 to 1.34; P = 0.30; I 2 , 0%). However, the incidence of miscarriage was not different between the oral dydrogesterone and vaginal progesterone groups., Conclusion: Progesterone therapy, especially oral dydrogesterone, can effectively prevent miscarriage in pregnant women experiencing threatened abortion.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

To investigate the clinical effect of Gushen Antai pills and progesterone in the treatment of threatened abortion, in order to provide references for early clinical intervention with threatened abortion. The 112 cases of patients with threatened abortion were randomly divided into the control group and the observation group. 56 cases in each group. Patients in the control group was injected with progesterone, the observation group was treated with Gushen Antai pills in addition to the therapy of the control group. Both groups were treated by drugs for two weeks. Their venous bloods (5 mL) were collected before treatment and in 1, 2 weeks after treatment to determine serum levels of β-HCG, P, E2 and CA125. The differences between the two groups after treatment were compared. The total effective rate of the control group and the observation group were 79% and 91.9% respectively, with a statistically significant difference between the two groups (P＜0.05). Two weeks after the treatment, the serum levels of P and E2 in the observation group were significantly higher than before treatment, but the serum CA125 levels decreased significantly after treatment (P<0.05). These indicators showed statistically significant difference compared with that of the control group (P<0.05). After treatment, the serum β-HCG levels of the two groups were significantly higher than before treatment (P<0.05), but there was no statistically significant difference between the two groups. Gushen Antai pills and progesterone had a better clinical curative effect in treatment threatened abortion, which could significantly raise serum β-HCG, P and E2, reduce serum CA125 and increase the tocolysis efficiency, and so it was worth promoted in clinic., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Chinese Pharmaceutical Association.)

This guideline has been developed based on studied and clinical investigations. Therefore, it appears to be appropriate to use all the available evidence, which are very encouraging, in a summarized form to propose guidelines by a group of European experts in order to give the gynecologists, obstetricians and reproductive medicine specialists have direction with regard to the prevention or treatment of miscarriage for the benefit of the endangered pregnancies. There are a number of statements, opinions and guidelines already published for this topic, which are not entirely in agreement.

Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese herbal medicine for threatened miscarriage. Potential reproductive toxicity of LAR was identified in early pregnancy in animals. Skeletal anomalies including loss of ulna and distal digits, shortening of humerus and radius were observed in higher clinical dose groups. Here, we aimed to study the molecular mechanism of the congenital malformation induced by LAR. In vitro whole mouse embryo culture was used to confirm the embryotoxicity effects of LAR on developing limb buds during early organogenesis. A pregnant mouse model was employed to study the developmental gene expression by quantitative PCR and whole hybridization and apoptosis by terminal deoxynucleotidyl transferase dUTP nick end labeling staining, in the forelimbs and hindlimbs during development in vivo. Severe growth retardation, multiple embryonic malformations and delayed limb bud development were observed. Limb-specific Tbx gene expressions in both developing forelimbs and hindlimbs were significantly decreased. Increased developmental apoptosis in apical ectodermal ridge and mesenchymal mesoderm of the developing limb buds was identified. Overexpressions of Tbx2 and Tbx3 in embryos in vitro rescued LAR-induced abnormal limb development and reduced apoptosis in the developing forelimb buds. In conclusion, LAR affects limb development by suppressing the expression of limb developmental genes and disturbing programmed cell death during limb formation in mice.

The objective of this systematic review was to assess whether the orally acting progestagen, dydrogesterone lowers the incidence of miscarriage in women with threatened miscarriage. A computerized search was performed in Medline, Embase, and Ovid Medline for original reports with the product name 'Duphaston' or 'dydrogesterone', and limited to clinical human data. Twenty-one reports of dydrogesterone treatment were identified with 1380 patients. Five randomized trials were identified, including 660 women who fulfilled the criteria for meta-analysis. The number of subsequent miscarriages or continuing pregnancies per randomized woman was compared in women receiving dydrogesterone compared to standard bed rest or placebo intervention. There was a 13% (44/335) miscarriage rate after dydrogesterone administration compared to 24% in control women [odds ratio for miscarriage 0.47, (CI = 0.31-0.7), 11% absolute reduction in the miscarriage rate]. The adverse and side effects were summarized in all 21 reports, and seemed to be minimal. Although all the predictive and confounding factors could not be controlled for, the results of this systematic review show a significant reduction of 47% in the odds for miscarriage when dydrogesterone is compared to standard care indicating a real treatment effect.

Blood levels of total Mg, ionized Mg and intracellular ionized Mg of platelet were lowered in the 2nd trimester of gestation and thereafter. Urinary excretion of Mg does not change during the whole period of pregnancy. According to our results of animal experiments, intestinal absorption of Mg does not increase during pregnancy compared with non-pregnant state. These data suggest pregnant women tend to become magnesium deficiency. This is reflected in the fact that Mg metabolic parameters of pregnant women with preeclampsia are relatively reduced compared with those of healthy gravidae. In the obstetrical practice Mg has other significance, because magnesium sulfate is frequently used as a drug of choice in the therapy of threatened premature delivery and eclampsia. Mg plays important roles in physiology and pharmacology during gestation.

Background: Threatened miscarriage occurs in 10% to 15% of all pregnancies. Vaginal spotting or bleeding during early gestation is common, with nearly half of those pregnancies resulting in pregnancy loss. To date, there is no effective preventive treatment for threatened miscarriage. Chinese herbal medicines have been widely used in Asian countries for centuries and have become a popular alternative to Western medicines in recent years. Many studies claim to show that they can prevent miscarriage. However, there has been no systematic evaluation of the effectiveness of Chinese herbal medicines for threatened miscarriage., Objectives: To review the therapeutic effects of Chinese herbal medicines for the treatment of threatened miscarriage., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (31 January 2012), Chinese Biomedical Database (1978 to 31 January 2012), China Journal Net (1915 to 31 January 2012), China National Knowledge Infrastructure (1915 to 31 January 2012), WanFang Database (1980 to 31 January 2012), Chinese Clinical Trial Registry (31 January 2012), EMBASE (1980 to 31 January 2012), CINAHL (31 January 2012), PubMed (1980 to 31 January 2012), Wiley InterScience (1966 to 31 January 2012), International Clinical Trials Registry Platform (31 January 2012) and reference lists of retrieved studies. We also contacted organisations, individual experts working in the field, and medicinal herb manufacturers., Selection Criteria: Randomised or quasi-randomised controlled trials that compared Chinese herbal medicines (alone or combined with other pharmaceuticals) with placebo, no treatment (including bed rest), or other pharmaceuticals as treatments for threatened miscarriage., Data Collection and Analysis: Two review authors independently assessed all the studies for inclusion in the review, assessed risk of bias and extracted the data. Data were checked for accuracy., Main Results: In total, we included 44 randomised clinical trials with 5100 participants in the review.We did not identify any trials which used placebo or no treatment (including bed rest) as a control.The rate of effectiveness (continuation of pregnancy after 28 weeks of gestation) was not significantly different between the Chinese herbal medicines alone group compared with the group of women receiving Western medicines alone (average risk ratio (RR) 1.23; 95% confidence interval (CI) 0.96 to 1.57; one trial, 60 women).Chinese herbal medicines combined with Western medicines were more effective than Western medicines alone to continue the pregnancy beyond 28 weeks of gestation (average RR 1.28; 95% CI 1.18 to 1.38; five trials, 550 women)., Authors' Conclusions: There was insufficient evidence to assess the effectiveness of Chinese herbal medicines alone for treating threatened miscarriage.A combination of Chinese herbal and Western medicines was more effective than Western medicines alone for treating threatened miscarriage. However, the quality of the included studies was poor. More high quality studies are necessary to further evaluate the effectiveness of Chinese herbal medicines for threatened miscarriage.

Background: Miscarriage is a common complication encountered during pregnancy. The role of progesterone in preparing the uterus for the implantation of the embryo and its role in maintaining the pregnancy have been known for a long time. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss., Objectives: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage., Search Methods: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 September 2011) and bibliographies of all located articles for any additional studies., Selection Criteria: Randomised or quasi-randomised controlled trials that compare progestogen with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage., Data Collection and Analysis: At least two authors assessed the trials for inclusion in the review, assessed trial quality and extracted the data. Data were checked for accuracy., Main Results: We included four studies (421 participants) in the meta-analysis. In three studies all the participants met the inclusion criteria and in the fourth study, we included only the subgroup of participants who met the inclusion criteria in the meta-analysis. There was evidence of a reduction in the rate of spontaneous miscarriage with the use of progestogens compared to placebo or no treatment (risk ratio (RR) 0.53; 95% confidence interval (CI) 0.35 to 0.79). There was no increase in the rate of antepartum haemorrhage (RR 0.76; 95% CI 0.30 to 1.94), or pregnancy-induced hypertension (RR 1.00; 95% CI 0.54 to 1.88) for the mother. The rate of congenital abnormalities was no different between the newborns of the mothers who received progestogens and those who did not (RR 0.70; 95% CI 0.10 to 4.82)., Authors' Conclusions: The data from this review suggest that the use of progestogens is effective in the treatment of threatened miscarriage with no evidence of increased rates of pregnancy-induced hypertension or antepartum haemorrhage as harmful effects to the mother, nor increased occurrence of congenital abnormalities on the newborn. However, the analysis was limited by the small number and the poor methodological quality of eligible studies (four studies) and the small number of the participants (421), which limit the power of the meta-analysis and hence of this conclusion.

Background: Largehead Atractylodes Rhizome (LAR) is the most commonly used Chinese medicine to prevent early pregnancy loss due to threatened miscarriage. However, its safety profile during pregnancy is still not available. Here we aimed to identify the potential adverse effects of LAR on embryo-fetal development as well as prenatal and post-natal growth., Methods: Pregnant mice, rats and rabbits were orally administered with LAR extracts in various doses (from 1×, 2×, 3× and up to 6× clinical doses) at different gestational periods (implantation, gastrulation, organogenesis, maturation and whole gestation). Maternal effects on weight loss, implantation failure and fetal resorption and perinatal effects on developmental delay, growth restriction and congenital malformations were studied., Results: In mice, with early LAR exposure, a significant decrease in fetal growth parameters and a significant increase in post-implantation loss were identified. With late LAR exposure, significant increases in gestational duration as well as prenatal and post-natal mortality were found. At high clinical doses, congenital skeletal malformations were recorded. In rabbits, fetal resorption, hydrops fetalis and short ear anomaly were observed. No significant adverse effects were found in rats., Conclusions: Potential reproductive toxicity of LAR in pregnant animals was identified within the clinical dose. Caution should be taken in clinical applications of LAR during pregnancy.

Background: Miscarriage is a common complication encountered during pregnancy. The role of progesterone in preparing the uterus for the implantation of the embryo and its role in maintaining the pregnancy have been known for a long time. Inadequate secretion of progesterone in early pregnancy has been linked to the aetiology of miscarriage and progesterone supplementation has been used as a treatment for threatened miscarriage to prevent spontaneous pregnancy loss., Objectives: To determine the efficacy and the safety of progestogens in the treatment of threatened miscarriage., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (December 2009) and bibliographies of all located articles for any unidentified articles., Selection Criteria: Randomized or quasi-randomized controlled trials that compare progestogen with placebo, no treatment or any other treatment given in an effort to treat threatened miscarriage., Data Collection and Analysis: At least two authors assessed the trials for inclusion in the review and extracted the data., Main Results: Two studies (84 participants) were included in the meta-analysis. In one study, all the participants met the inclusion criteria and in the other study, only the subgroup of participants who met the inclusion criteria was included in the meta-analysis. There was no evidence of effectiveness with the use vaginal progesterone compared to placebo in reducing the risk of miscarriage (risk ratio 0.47; 95% confidence interval 0.17 to 1.30)., Authors' Conclusions: Based on scarce data from two methodologically poor trials, there is no evidence to support the routine use of progestogens for the treatment of threatened miscarriage. Information about potential harms to the mother or child, or both, with the use of progestogens is lacking. Further, larger, randomized controlled trials on the effect of progestogens on the treatment of threatened miscarriage, which investigate potential harms as well as benefits, are needed.

Background: Miscarriage is a common occurrence in early pregnancy. Human chorionic gonadotrophin (hCG) is secreted by the syncytiotrophoblast. It promotes the corpus luteum to secrete progesterone and helps in maintaining the pregnancy. Hence, there has been much interest in the use of hCG to treat threatened miscarriage., Objectives: To assess the efficacy and safety of human chorionic gonadotropins in the treatment of threatened miscarriage., Search Strategy: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (February 2010), the Cochrane Central Register of Controlled Trials (The Cochrane Library 2010, Issue 1), MEDLINE (1966 to 12 February 2010), EMBASE (1980 to 12 February 2010) and CINAHL (1989 to 12 February 2010). We also scanned the bibliographies of all located articles for any unidentified articles and attempted to contact authors where necessary., Selection Criteria: All randomised controlled trials (RCTs) that assess the effectiveness of hCG in the treatment of threatened miscarriage compared to placebo, no treatment of any other intervention, provided viability of the fetus has been confirmed by ultrasound before the commencement of treatment., Data Collection and Analysis: At least two authors assessed the trials for inclusion in the review and extracted the data., Main Results: Three studies (312 participants) were included in the review, one of which was of poor methodological quality. The meta-analysis showed that there was no statistically significant difference in the incidence of miscarriage between hCG and 'no hCG' (placebo or no treatment) groups (Risk ratio (RR) 0.66; 95% confidence interval (CI) 0.42 to 1.05). When hCG and bed rest alone were compared, there was a significant reduction in the risk of miscarriage (RR 0.47; 95% CI 0.27 to 0.82). This result should be interpreted with caution, as one of the two trials from which this result is derived was of poor methodological quality. There was no report of adverse effects of hCG on mother or baby. More good quality RCTs are urgently needed to assess the effects of hCG in threatened miscarriage., Authors' Conclusions: The current evidence does not support the routine use of hCG in the treatment of threatened miscarriage.

Progesterone supplementation has been used in a large number of women with threatened abortion for decades, despite various degrees of success, and contradictory and ever-changing views about its efficacy. The majority of previous literature has mainly focused on evaluation the effect of progesterone on pregnancy outcome of threatened abortion. No controlled epidemiological studies of obstetric and perinatal outcomes, including preterm birth, pregnancy complications and low birth weight newborns, in pregnant women with progesterone treatment have been published. The data of 523 pregnant women with progesterone treatment in the second and third months of pregnancy due to threatened abortion was compared with the data of other 21,054 pregnant women in the Department of Obstetrics, West China Second University Hospital for a period of 6years from January 2002 to October 2008. There was no difference in mean gestational age at delivery and birth weight, in addition the rate of preterm birth, pregnancy complications and low birth weight newborns. Intramuscular progesterone treatment due to threatened abortion during early pregnancy did not associate with a higher risk for pregnancy complications, preterm birth and low birth weight newborns.

Threatened miscarriage, as demonstrated by vaginal bleeding with or without abdominal cramps, is a common complication of pregnancy. It occurs in about 20% of recognised pregnancies. Risk of miscarriage is increased in older women and those with a history of miscarriage. Low serum levels of progesterone or human chorionic gonadotrophin (hCG) are a risk factor for miscarriage. Other risk factors include heavy bleeding, early gestational age and an empty gestational sac of >15-17 mm diameter. Clinical history and examination, maternal serum biochemistry and ultrasound findings provide valuable information about the prognosis and are important to establish in order to determine potential treatment options. Although bed rest is the most common choice of treatment, there is little evidence of its value. Other options include luteal support with progesterone, dydrogesterone or hCG. There is some evidence from clinical studies indicating that progesterone or dydrogesterone may reduce the rate of miscarriage, although further data from double-blind, randomised-controlled trials are necessary to confirm efficacy., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)

Introduction: Threatened miscarriage is a common problem during pregnancy., Methods: The aim of this prospective, open, randomised study was to determine whether dydrogesterone was more effective than conservative management alone in preventing miscarriage in women with vaginal bleeding up to week 16 of pregnancy. Women were excluded if they had a history of recurrent miscarriage. A total of 191 women were randomised to dydrogesterone (40 mg stat followed by 10mg twice daily) or conservative management (control group). The treatment was considered successful if the pregnancy continued beyond 20 weeks of gestation., Results: The success rate in the dydrogesterone group was statistically significantly higher than that in the control group (87.5% vs. 71.6%; p<0.05). Miscarriage occurred in 12.5% of women in the dydrogesterone group compared with 28.4% in the control group (p<0.05). There were no differences between the groups with regard to the incidence of Caesarean section, placenta praevia, antepartum haemorrhage, preterm labour (weeks 28-36), pregnancy-induced hypertension or low birth weight (<2500 g) babies. There were no intrauterine deaths or congenital abnormalities in either group., Conclusion: Compared with conservative management, dydrogesterone had beneficial effects on maintaining pregnancy in women with threatened miscarriage., (Copyright 2009 Elsevier Ireland Ltd. All rights reserved.)