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.

A rapid improvement event: progesterone prescribing in prevention of miscarriage.

A rapid improvement event (RIE) is a standard operational excellence technique that uses team-based problem solving to improve processes. In this study, a RIE was undertaken to improve progesterone prescribing rates for those with a history of miscarriage experiencing vaginal bleeding in early pregnancy. This was on the basis of a recent change in guidelines regarding prescribing in these instances. NICE guidelines changed in November 2021 after Cochrane meta-analysis and the PRISM (Progesterone in Spontaneous Miscarriage) randomised control trial demonstrated a higher incidence of live births in those prescribed vaginal micronised progesterone for threatened miscarriage, when compared with those not prescribed it.A RIE involves a team approach and a standard sequence of events allowing analysis and improvement of a process. Analysis in the form of audit revealed a low progesterone prescribing rate for eligible patients in our unit. Dissection of this problem into its elements revealed a low level of staff knowledge regarding the change in guidelines and a lack of confidence in prescription of progesterone. A plan of actionable events to improve prescribing rates was devised. The updated guidance and local recommendations on appropriate micronised progesterone formulations were presented at hospital Grand Rounds with multidisciplinary attendance. Infographics were displayed in areas visible to stakeholders within the hospital and on the hospital's social media pages. The validity of these educational measures to improve the process was reaudited after 3 months.Progesterone prescribing improved by 48%. Those comfortable with prescribing as per the new guidelines improved from 43% to 78%. A RIE proved to be an effective and efficient approach to collaboration, decision-making and action.

Recurrent miscarriage: green-top guideline nº 17

The purpose of this guideline is to provide guidance on the investigation and care of women and people with recurrent miscarriage.Within this document we use the terms woman and women's health. However, it is important to acknowledge that it is not only women for whom it is necessary to access women's health and reproductive services in order to main-tain their gynaecological health and reproductive wellbeing. Gynaecological and obstetric services and delivery of care must therefore be appropriate, inclusive and sensitive to the needs of those individuals whose gender identity does not align with the sex they were assigned at birth. The term cou-ple is used to describe two individuals trying to conceive, recognising that in some instances these individuals may not be in a relationship. While every effort is made to ensure the RCOG uses inclusive language there are instances where we have been unable to adhere to this, for example where original research is being referenced the language within the publication is used for accuracy.

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).

Real-world pharmacological treatment patterns of patients with threatened miscarriage in China from 2014 to 2020: A cross-sectional analysis.

WHAT IS KNOWN AND OBJECTIVE: Approximately half of the patients with threatened miscarriage suffer an abortion, and consistent medication therapy to prevent threatened miscarriage is lacking. Our goal was to investigate the real-world pharmacological treatment patterns of patients with threatened miscarriage in China, with a focus on the trend and rationality of progestogen use over the last 7 years. METHODS: We performed a cross-sectional analysis of data from the Hospital Prescription Analysis Cooperation Project that is overseen by the Chinese Pharmaceutical Association. Information was extracted from prescriptions of outpatients with threatened miscarriage between January 2014 and December 2020. We quantified the types of medications using the first level anatomical therapeutic chemical (ATC) classification code and the frequency of use of medicines classified as category X by the United States Food and Drug Administration (FDA). We also calculated the prevalence of the most frequently used progestogens by assessing prescription rates, determined the sum of the defined daily doses (DDDs) and defined daily cost (DDC) and evaluated the rationality of progestogens according to drug labels and guidelines. RESULTS AND DISCUSSION: Of the 91,464 patients included in this study, 69.4% were from the eastern region, 92.5% were from tertiary hospitals, and 72.9% were between 25 and 34 years old. The average number of medications per patient was 1.4. The following types of medicines were the most prevalent: "genitourinary system and sex hormones" (90.7%), "alimentary tract and metabolism" (10.8%) and "blood and blood-forming organs" (9.9%). Progestogens were prescribed for 81,080 patients (88.6%), among which oral progesterone (39.7%) was the most commonly used, followed by oral dydrogesterone (34.4%), progesterone injection (26.0%), oral allylestrenol (0.7%) and progesterone gel (0.4%). In other words, 10,991 (12.0%) patients used more than one progestogen, and the top three combinations were oral dydrogesterone plus progesterone injection (5.6%), oral progesterone plus progesterone injection (4.7%) and oral dydrogesterone plus oral progesterone (1.1%). The prescription rate of dydrogesterone increased gradually, whereas that of progesterone, especially progesterone injection, obviously decreased. Among 34,760 prescriptions of progestogens with complete usage information, the primary errors of progestogen use were "low frequency" (18.4%), "high single dose" (15.9%) and "low single dose" (11.3%). In addition, 137 prescriptions were identified with drug-progestogen interactions, and 61 were identified with contraindications for progestogens. A total of 4.5% of prescriptions included FDA category X medicines. WHAT IS NEW AND CONCLUSION: Our findings are the first to provide information on medication use in patients with threatened miscarriage over the last seven years in China. Medicines targeting the "genitourinary system and sex hormones," especially progestogens, were the most commonly prescribed medications, among which dydrogesterone was the most prevalent. However, it is remarkable that the use of progestogens for the treatment of threatened abortion is still controversial; thus, high-quality large sample studies are still required, especially among Chinese patients. Since usage errors in progestogen records and exposure to category X medicines were common, more efforts are needed to guarantee the safety and rationality of medicines used in pregnant women.

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.

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.

Sporadic pregnancy loss and recurrent miscarriage.

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.

[Effect on immune factors and serum CA125 in patients of threatened abortion in early pregnancy complicated with subchorionic hematoma treated with auricular acupuncture combined with dydrogesterone].

OBJECTIVE: To evaluate the therapeutic effect of auricular acupuncture combined with dydrogesterone for threatened abortion in early pregnancy complicated with subchorionic hematoma. METHODS: A total of 80 patients were randomized into an observation group and a control group, 40 cases in each one. In the control group, dydrogesterone was taken orally twice a day, 10 mg a time until 12-week into pregnancy. In the observation group，auricular acupuncture was applied at penqiang (TF5), pizhixia (AT4), shen (CO10), xin(CO15), gan (CO12), jiaogan (AH6a) and neifenmi (CO18) on the basis of the control group, the auricular points on both sides were used alternatively. The auricular points were replaced every 3 days with 1 day break, totally 3 weeks (20 days) were required. Before treatment and after 10, 20 days of treatment, the percentage of helper T lymphocyte (Th) and inhibitory T lymphocyte (Ts), ratio of Th and Ts and serum level of CA125 were compared in the two groups. The areas of subchorionic hematoma and gestational sac were evaluated by B ultrasound. The therapeutic effect in the two groups were compared. RESULTS: The effective rate in the observation group was 80.0% (32/40), which was superior to 65.0% (26/40) in the control group (P<0.05). After 10, 20 days of treatment, the percentage of Th and ratio of Th and Ts were lower than before treatment, the percentage of Ts were increased in the two groups (P<0.01). After 20 days of treatment, the percentage of Th and ratio of Th and Ts in the observation group were lower than the control group (P<0.01), the percentage of Ts was higher than the control group (P<0.01). After 10, 20 days of treatment, the serum levels of CA125 were reduced compared before treatment in the two groups (P<0.01), and the serum levels of CA125 in the observation group were lower than the control group (P<0.01). After 10, 20 days of treatment, the ratio of subchorionic hematoma area and gestational sac area in the observation group was lower than the control group (P<0.01). CONCLUSION: Auricular acupuncture combined with dextroprogesterone can improve the effective rate of patients with threatened abortion in early pregnancy complicated with subchorionic hematoma, regulate immune factors, promote the hematoma absorption, and has a better synergistic effect with dextroprogesterone.

The predictive value of serum cancer antigen 125 (CA125) levels on pregnancy outcome in threatened miscarriages.

Background Spontaneous miscarriages are common pregnancy complications which result in psychological and emotional burden in the affected women. It is therefore necessary to identify biomarkers that can predict pregnancy outcome in women with threatened miscarriages so as to assist in their counselling and management. Methods The study compared levels of maternal serum CA125 in 65 pregnancies with threatened miscarriages (study group) with 65 normal intrauterine pregnancies (control group) between 6 weeks and 19 weeks + 6 days gestation using an enzyme linked immunosorbent assay (ELISA) technique. Results The mean age of the study and control groups were 29.5 ± 0.14 years and 30.1 ± 0.14 years, respectively. The mean serum CA125 in the study group was 30.1 ± 1.1 IU/mL while that of the control group was 22.9 ± 1.2 IU/mL and this was statistically significant (P = 0.0001). The mean serum CA125 level in the women whose pregnancies were aborted (aborters) was 34.8 ± 1.4 IU/mL while the mean value among those whose pregnancies continued till term (non-aborters) was 27.3 ± 1.2 IU/mL. This was statistically significant (P = 0.001). Further analysis using CA125 ≥36.2 IU/mL (mean value of serum CA125 among aborters + 1 standard deviation) as a threshold for intrauterine pregnancies that eventually got aborted showed a sensitivity of 66.7%, specificity of 83.3%, positive predictive value of 55.6%, negative predictive value of 88.9% and the diagnostic effectiveness (accuracy) was 79.4%. Conclusion The measurement of serum CA125 is a useful predictor of pregnancy outcome in threatened miscarriages.

[Adjuvant therapy of acupoint catgut embedding for threatened abortion after in vitro fertilization-embryo transfer: a randomized controlled trial].

OBJECTIVE: To observe the effects of acupoint catgut embedding on miscarriage prevention and pregnancy outcome in patients with threatened abortion after in vitro fertilization-embryo transfer (IVF-ET). METHODS: Sixty cases of patients with threatened abortion after IVF-ET were randomly divided into an observation group and a control group, 30 cases in each group. The patients in the control group were treated with intramuscular injection of progesterone (40 mg) once every day, while the patients in the observation group, on the basis of the treatment of control group, were treated with catgut embedding at Geshu (BL 17), Ganshu (BL 18), Shenshu (BL 23), Pishu (BL 20), Weishu (BL 21), Xuehai (SP 10), Diji (SP 8) and Fuliu (KI 7), once every two weeks, six times as a course of treatment. The treatment was given until 12 weeks into pregnancy. The level of serum human chorionic gonadotropin (HCG), estradiol (E2) and progesterone (P) before and after treatment was recorded; the TCM syndrome score before and after treatment was compared; the successful pregnancy rate and spontaneous abortion rate after treatment were observed in the two groups. RESULTS: Compared before treatment, the scores of TCM syndrome in both groups were reduced after treatment (both P<0.01), and score in the observation group was superior to that in the control group (P<0.05). After treatment, the clinical efficacy in the observation group was superior to that in the control group (P<0.05). After treatment, the hormone levels (ß-HCG, E2, P) in both groups were increased steadily; the hormone levels in 6-week pregnancy, 8-week pregnancy and 10-week pregnancy were significantly higher than those in 4-week pregnancy (all P<0.05); except the levels of P and ß-HCG in 10-week pregnancy, the hormone levels in the observation group were superior to those in the control group (all P<0.05). After treatment, the early abortion rate was 16.7% (5/30) in the observation group, which was lower than 33.3% (10/30) in the control group (P<0.01); the pregnancy rate was 96.0% (24/25) in the observation group, which was higher than 80.0% (16/20) in the control group (P<0.01). CONCLUSION: Acupoint catgut embedding is effective for preventing threatened abortion, which could significantly reduce the spontaneous abortion rate, improve the pregnancy success rate, regulate hormone levels in patients after IVF-ET.

[The prevent miscarriage effects of Yun Kang oral liquid on threatened abortion rat induced by kidney deficiency and luteum inhibition].

OBJECTIVE: Yun Kang oral liquid is a listed proprietary Chinese Medicine. To further evaluate its efficacy, this experiment established a kidney deficiency and luteum inhibition threatened abortion rat model to observe the effects of Yun Kang oral liquid. METHODS: Sixty pregnant rats were randomly divided into normal control group (NC), model group (MG), dydrogesterone group (DT, 3.02 mg/kg), and Yun Kang oral liquid low-dose group (YK-L, 4 ml/kg), medium dose group (YK-M, 6 ml/kg), high dose group (YK-H, 9 ml/kg), 10 in each group. On the first day of pregnancy, each administration group was treated with the test drug at the prescribed dose every morning, and the NC group and the MG group were given an equal volume of purified water for 10 days; the rats were intragastrically administrated every afternoon, except for the NC group. In addition, the other groups were intragastrically administered with hydroxyurea at a dose of 450 mg/kg for 9 days, and mifepristone was administered at a dose of 4.0 mg/kg on the 10th day. On the 9th day of pregnancy, behavioral signs such as back temperature, grasping force, pain threshold, and autonomic activity were measured in each group. On the 11th day of pregnancy, blood was collected from the abdominal aorta in each group to determine serum levels of estradiol (E2) , progesterone (P) and thromboxane B2 (TXB2) . Ovary and fetal uterus were removed, the number and diameter of embryos were observed, and the ovary and uterus indexes were calculated. RESULTS: Compared with the NC group, the back temperature, grip, pain threshold, number of spontaneous activities, number of embryos, embryo diameter, uterus index and serum E2, P, TXB2 levels in the MG group were decreased significantly (P＜0.05, 0.01). Compared with the MG group, the back temperature, grasping force, number of embryos, embryo diameter and serum E2 and P levels were increased significantly in each dose group (P＜0.05, 0.01); the pain threshold, autonomic activity, and uterus index of YK-M and YK-H group were increased significantly (P＜0.05); serum level of TXB2 in YK-H group were increased significantly (P＜0.05). CONCLUSION: Yun Kang oral liquid has a clear kidney-filling effect on rats with threatened abortion caused by kidney deficiency-luteal suppression. The mechanism may be related to raising serum E2, P, TXB2 levels, improving kidney deficiency and improving embryo quality.

Efficacy of progesterone on threatened miscarriage: Difference in drug types.

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.

Alpha lipoic acid in obstetrics and gynecology.

Alpha-Lipoic acid (ALA) is a natural antioxidant synthetized by plants and animals, identified as a catalytic agent for oxidative decarboxylation of pyruvate and α-ketoglutarate. In this review, we analyzed the action of ALA in gynecology and obstetrics focusing in particular on neuropathic pain and antioxidant and anti-inflammatory action. A comprehensive literature search was performed in PubMed and Cochrane Library for retrieving articles in English language on the antioxidant and anti-inflammatory effects of ALA in gynecological and obstetrical conditions. ALA reduces oxidative stress and insulin resistance in women with polycystic ovary syndrome (PCOS). The association of N-acetyl cysteine (NAC), alpha-lipoic acid (ALA), and bromelain (Br) is used for prevention and treatment of endometriosis. In association with omega-3 polyunsaturated fatty acids (n-3 PUFAs) with amitriptyline is used for treatment of vestibulodynia/painful bladder syndrome (VBD/PBS). A promising area of research is ALA supplementation in patients with threatened miscarriage to improve the subchorionic hematoma resorption. Furthermore, ALA could be used in prevention of diabetic embryopathy and premature rupture of fetal membranes induced by inflamation. In conclusion, ALA can be safely used for treatment of neuropatic pain and as a dietary support during pregnancy.

Progestogens and pregnancy loss.

Progestational agents are often prescribed to prevent pregnancy loss. Progestogens affect implantation, cytokine balance, natural killer cell activity, arachidonic acid release and myometrial contractility. Progestogens have therefore been used at all stages of pregnancy including luteal-phase support prior to pregnancy, threatened miscarriage, recurrent miscarriage, and to prevent preterm labor. In luteal support, a Cochrane review reported that progestogens were associated with a higher rate of live births or ongoing pregnancy in the progesterone group (odds ratio 1.77, 95% confidence interval (CI) 1.09-2.86). Evidence suggests that progestogens are also effective for treating threatened miscarriage. Again, in a Cochrane Database review, progestogens were associated with a reduced odds ratio of 0.53 (95% CI 0.35-0.79) when progestogens were used. In recurrent miscarriage, progestogens also seem to have a beneficial effect. A meta-analysis of progestational agents showed a 28% increase in the live birth rate (relative risk 0.72, 95% CI 0.53-0.97). For the last 30 years, progestogens have been used to prevent preterm labor. Recent meta-analyses also report beneficial effects. This review summarizes the literature and the author's experience using progestogens to prevent pregnancy loss.

Outcomes of threatened abortions after anticoagulation treatment to prevent recurrent pregnancy loss.

We aimed to determine the outcome of threatened abortion in women treated with low-molecular weight heparin (LMWH) for recurrent pregnancy loss (RPL). Data of women with RPL who experienced threatened abortion while taking LMWH between 2007 and 2016 were retrospectively reviewed. All patients received the LMWH, enoxaparin (40 mg). Thrombophilia was present in 38 (33.3%) women, including 11 (9.6%) with antiphospholipid syndrome (APLS). The overall live birth rate was 58.8% (67/114). Live birth rates were 87.2% (41/47 patients) and 38.8% (26/67 patients) among those who discontinued versus those who continued LMWH treatment, respectively (P < 0.0001). Among APLS patients, live births resulted in eight of the nine women who continued LMWH. In multivariate analysis, discontinuation of LMWH was the only significant predictor of live birth outcome (P < 0.0001). Thrombophilia, presence of subchorionic haematoma, and severity of bleeding were not found to be associated with live birth outcomes. For women with threatened abortions, continuation of LMWH indicated to prevent RPL was negatively associated with live birth rates. Therefore, we support its discontinuation in this setting. Among women with APLS, LMWH continuation resulted in a relatively high live birth rate; we advocate against its withdrawal in this subset of patients.

The Influence of Oral Dydrogesterone and Vaginal Progesterone on Threatened Abortion: A Systematic Review and Meta-Analysis.

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; I2, 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; I2, 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; I2, 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.

Is progestogen supplementation necessary to prevent abortion?

A prospective study was conducted to evaluate the effect of progestogens on the pregnancy outcome of threatened abortion (TA). A total of 251 pregnant women less than 20 weeks of gestational age (GA) were included. Group 1 consisted of women with vaginal bleeding who had already been under treatment with progestogens and Group 2 was composed of women with vaginal bleeding who were only followed without progestogen therapy, whereas Group 3 was the control group without any vaginal bleeding or progestogen therapy. The pregnancy outcomes and serum progesterone levels were compared among the groups. The mean serum progesterone concentrations were statistically significantly higher in Group 1 in comparison to Group 2 and 3 (p < 0.001). Abortion rates were similar among the study groups. Although progestogen supplementation leads to increased level of serum progesterone, this finding does not translate to its beneficial effect on the pregnancy outcomes in cases of TAs.

A randomized double-blind controlled trial of the use of dydrogesterone in women with threatened miscarriage in the first trimester: study protocol for a randomized controlled trial.

BACKGROUND: Miscarriage is a common complication of pregnancy occurring in 15-20 % of all clinically recognized pregnancies. Currently, there is still no good scientific evidence to support the routine use of progestogens for the treatment of threatened miscarriage because the existing studies were not large enough to show a significant difference and some of them were not randomized or double-blind. METHODS: This is a double-blind, randomized controlled trial. A total of 400 patients presenting with first-trimester threatened miscarriage will be enrolled. They will be randomized to take dydrogesterone 40 mg per os, followed by 10 mg per os three times a day or placebo until twelve completed weeks of gestation or 1 week after the bleeding has stopped, whichever is longer. The primary outcome is the percentage of miscarriage before 20 weeks of gestation. DISCUSSION: We postulate that the dydrogesterone therapy will significantly reduce the risk of miscarriage in women with threatened miscarriage. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT02128685 . Registered on 29 April 2014.