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.

Evaluation of serum level of C-reactive protein (CRP) and its correlation with fetal ultrasound parameters in the prediction of threatened miscarriage in the first trimester.

BACKGROUND: Pregnancy loss occurring before 20 weeks gestation is referred to as miscarriage. Various clinical presentations of miscarriage include threatened, inevitable, incomplete, complete, septic, and missed miscarriage. Early-stage threatened miscarriage may manifest with symptoms such as abdominal discomfort and vaginal bleeding. Threatened miscarriage is clinically defined as the manifestation of positive fetal heart sounds in pregnancies occurring before the 20th week of gestation, concomitant with vaginal bleeding and a closed cervix. OBJECTIVES: The primary aim of this study was to evaluate the association between serum C-reactive protein (CRP) levels and fetal ultrasound findings in the prediction of threatened miscarriage during the first trimester of pregnancy. METHODS: In this prospective case-control study, a total of 100 pregnant women at 7-13 weeks of gestation were enrolled. All participants initially presented with a singleton embryo displaying cardiac activity on ultrasound. The study cohort was divided into two groups: Group 1 consisted of 50 women with uncomplicated pregnancies, while Group 2 comprised 50 women experiencing symptoms indicative of threatened miscarriage. RESULTS: Notably, within Group 2, patients who eventually experienced miscarriage exhibited significantly elevated serum high-sensitivity CRP levels in comparison to those who maintained their pregnancies. CONCLUSIONS: Threatened miscarriage cases demonstrated a substantial increase in serum high-sensitivity CRP levels compared to the control group. Furthermore, CRP levels exhibited a correlation with the risk of miscarriage, suggesting their potential utility in conjunction with ultrasound parameters for prognosticating threatened miscarriage during the first trimester.

Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta-analysis.

INTRODUCTION: Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta-analysis to assess the effectiveness and safety of progestogens for these patients. MATERIAL AND METHODS: We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk-of-bias tool and the certainty of evidence using the GRADE approach. RESULTS: Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99-1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97-1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96-1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98-1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01-1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76-1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83-1.40, absolute increase 0.2%, moderate certainty). CONCLUSIONS: In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.

Can single progesterone concentration predict miscarriage in early pregnant women with threatened miscarriage: a systematic review and meta-analysis.

BACKGROUND: About 25% of pregnant women experience bleeding in the early stage, and half of them eventually progress to pregnancy loss. Progesterone serves as a useful biomarker to predict miscarriage in threatened miscarriage, yet its performance is still debated. AIM: To evaluate the performance of single serum progesterone predicting miscarriage in early pregnant patients with threatened miscarriage. METHOD: The online database was searched to yield the literature using the terms of 'Abortion', 'Miscarriage', and 'serum Progesterone', including PubMed, Scopus, Embase, Cochrane library, and China national knowledge infrastructure. Receiver operating characteristic (ROC) curve, likelihood ratio (LLR) and diagnostic odds ratio (DOR) and 95% confidence interval (CI) were computed. Publication bias was assessed by the deeks funnel plot asymmetry test. Subgroup analyses were conducted according to the progesterone level (< 12 ng/mL), recruited location and region, progesterone measurement method, exogenous progesterone supplement and follow up. RESULTS: In total, 12 studies were eligible to be included in this study, with sample sizes ranging from 76 to 1087. The included patients' gestational age was between 4 and 12 weeks. No significant publication bias was detected from all included studies. The threshold of progesterone reported ranged from 8 to 30 ng/ml. The synthesized area under the ROC curve (0.85, 95% CI 0.81 to 0.88), positive LLR (6.2, 4.0 to 9.7) and DOR (18, 12 to 27) of single progesterone measurement distinguishing miscarriage were relatively good in early pregnant patients with threatened miscarriage. When the threshold of < 12 ng/mL was adapted, the progesterone provided a higher area under the ROC curve (0.90 vs. 0.78), positive LLR (8.3 vs. 3.8) and DOR (22 vs.12) than its counterpart (12 to 30 ng/mL). CONCLUSION: Single progesterone measurement can act as a biomarker of miscarriage in early pregnant patients with threatened miscarriage, and it has a better performance when the concentration is <12 ng/mL. TRIAL REGISTRATION: PROSPERO (CRD42021255382).

An evaluation of serum blood parameters and amyloid A levels in pregnant women with threatened miscarriage.

OBJECTIVE: This study investigated whether serum amyloid A (AA) levels can be used as a biomarker in patients with threatened abortion. MATERIAL AND METHODS: This prospective cohort study was conducted at the Antalya Training and Research Hospital, Department of Obstetrics and Gynecology, Türkiye, between April and October 2023. Eighty-eight pregnant women, 44 diagnosed with threatened miscarriage (Group 1) and 44 healthy individuals (Group 2), were included in the study. Sociodemographic, obstetric, and laboratory parameters were compared between the groups. RESULTS: No statistically significant differences were observed between the groups in terms of sociodemographic data (age, body mass index, education level, economic status, occupation status, smoking, and alcohol consumption). However, obstetric characteristics (number of pregnancies, living children, miscarriages, dilatation and curettage, gestational age on admission, and fetal crown-rump length) and laboratory values including complete blood count, hematocrit, leukocyte, neutrophil, lymphocytes, platelet, hs-C-reactive protein, neutrophil-lymphocyte and platelet-lymphocyte ratio (p > .05), and serum AA values (7.49 ± 3.07 in Group 1 vs. 9.46 ± 4.80 in Group 2, p = .024) differed significantly. Receiver operating characteristic analysis showed that the area under the curve (AUC: 0.662) was statistically significant for serum AA (p = .032), with a cut-off value of ≥7.51 (95% [confidence interval] 0.516-0.749, sensitivity 65%, specificity 51%). The positive predictive value of serum AA for threatened miscarriage was 56.8%, and the negative predictive value 59.4%. CONCLUSION: This study shows that serum AA can be used as a biomarker in the diagnosis of threatened miscarriage. Prospective studies involving more participants are now needed to confirm our results.

The Association of High-Molecular-Weight Hyaluronic Acid (HMWHA), Alpha Lipoic Acid (ALA), Magnesium, Vitamin B6, and Vitamin D Improves Subchorionic Hematoma Resorption in Women with Threatened Miscarriage: A Pilot Clinical Study.

Background-We evaluated whether the oral intake of high-molecular-weight hyaluronic acid (HMWHA) in association with alpha lipoic acid (ALA), magnesium, vitamin B6, and vitamin D can improve the resorption of subchorionic hematoma in cases of threatened miscarriage. Methods-In this study, we enrolled 56 pregnant women with threatened miscarriage (i.e., subchorionic hematomas, pelvic pain/uterine contractions, and/or vaginal bleeding) between the 6th and the 13th week of gestation. They were treated with vaginal progesterone (200 mg/twice a day) (control group; n = 25) or vaginal progesterone plus oral 200 mg HMWHA, 100 mg ALA, 450 mg magnesium, 2.6 mg vitamin B6, and 50 mcg vitamin D (treatment group; n = 31; DAV®-HA, LoLi Pharma srl, Rome, Italy). An ultrasound scan was performed at the first visit (T0) and after 7 days (T1) and 14 days (T2) until hematoma resorption. Results-At the ultrasound scan, the treatment group showed faster resorption of the subchorionic hematoma compared with the control group, both at T1 (control group 140 (112-180), treated group 84 (40-112), p < 0.0031), and T2 (control group: 72 (48-112), treated group: 0 (0-0), p < 0.0001). Moreover, subjective symptoms, such as vaginal bleeding, abdominal pain, and uterine contractions, showed a faster decrease in the treatment group than in the control group. Conclusions-The association may more rapidly improve the resolution of threatened miscarriage and related symptoms compared to the standard local protocol.

The Association between Threatened Miscarriage and Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder in Offspring by Age 14 Years.

OBJECTIVE: To examine the association between threatened miscarriage, and neurodevelopmental disorders, including autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) in offspring by age 14 years. METHODS: We used data from the Millennium Cohort Study, a nationally representative longitudinal study of children born in the UK. Data on threatened miscarriage and potential confounders were maternal-reported and collected at 9 months postpartum. Data on ASD and ADHD were based on maternal-reported doctor diagnoses and collected when children were aged 5, 7, 11 and 14 years. A diagnosis of ASD or ADHD was assumed if parents reported ASD or ADHD at age 5, 7, 11 or 14 years. Crude and adjusted logistic regression examined threatened miscarriage and ASD and ADHD relationship, adjusting for several sociodemographic, maternal and lifestyle factors. RESULTS: A total of 18,294 singleton babies were included at baseline, and 1,104 (6.0%) women experienced a threatened miscarriage during their pregnancy. Adjusted results suggested an association between threatened miscarriage and ASD (OR: 1.55, 95% CI 1.15, 2.08), and ADHD (OR: 1.51, 95% CI 1.09, 2.10) by age 14 years. E-values for threatened miscarriage and ASD were 2.47, while the lower limits of the 95% CI were 1.57. E-values for threatened miscarriage and ADHD were 2.39, while the corresponding lower limits of the 95% CI were 1.40. CONCLUSION: Threatened miscarriage was associated with an increased likelihood of ASD and ADHD by the age of 14 years, however, residual confounding cannot be ruled out. Placental pathology may be a potential mechanism for the observed associations.

Progesterone after mifepristone: A pilot prospective single arm clinical trial for women who have changed their mind after commencing medical abortion.

AIM: This pilot study aimed to assess the utility of an oral progesterone treatment protocol for women who commenced medical abortion and then changed their mind and wished instead to maintain their pregnancy. METHODS: The Progesterone-After-Mifepristone-pilot for efficacy and reproducibility (PAMper) trial was designed as a prospective single-arm pilot clinical trial, conducted via telehealth. Women aged 18 to 45 years in Australia who reported ingesting mifepristone within the last 72 h to initiate medical abortion and had not taken misoprostol were included. Initial contact was by a web-based form. Following informed consent, participants were prescribed oral progesterone to be taken 400 mg twice per day for 3 days then 400 mg at night until completion of a 19 day course. Pregnancy viability was assessed by ultrasound scan after 14 days of progesterone treatment. RESULTS: Between October 2020 and June 2021, nine women contacted the PAMper trial, of whom six enrolled and commenced progesterone treatment. These women reported ingesting mifepristone at 40-70 days of gestation, with progesterone being commenced within 5.7-72 h of mifepristone ingestion. Five participants had ongoing, live pregnancies at the primary endpoint (ultrasound at >2 weeks). One participant had a miscarriage after 9 days of progesterone treatment. There were no clinically significant adverse events. CONCLUSION: This small study demonstrated a clinically sound protocol for researching the use of progesterone-after-mifepristone for women in this circumstance. Results of this pilot study support the need for further larger scale trials in this field.

Study on the protective effect and mechanism of soybean isoflavones against threatened miscarriage model rats / 中国药房

OBJECTIVE To study the protective effect and possible mechanism of soybean isoflavones against threatened miscarriage rats. METHODS Female mice were selected to promote estrus and mate with male mice. After pregnancy， they were randomly divided into normal group （purified water， i.g.， n＝10）， model group （purified water， i.g.， n＝9）， positive control drug group （progesterone 4 mg/kg， i.m.， n＝9）， low-， medium- and high-dose soybean isoflavone groups （25， 50 and 100 mg/kg， i.g.， n＝10）. Except for the normal group， the rest were given mifepristone+misoprostol on the 8th day of pregnancy to establish threatened miscarriage model， and then given purified water or drugs， once a day， on days 1-7 and 9-12 of pregnancy， respectively. At 14 days of pregnancy， the rates of fetal protection were counted. Serum levels of β-human chorionic gonadotrophin （β-HCG） and progesterone （P） in rats were detected. Pathological and morphological changes in rat placenta and decidua tissues were observed， and the apoptosis indexes of cells were detected； mRNA and protein expressions of factor of apoptosis related （Fas）， factor of apoptosis related ligand （FasL）， proliferating cell nuclear antigen （PCNA） and heparin binding epidermal growth factor （HB-EGF） were determined in placenta tissues， and mRNA and protein expressions of Fas， PCNA and HB-EGF in decidua tissues were detected. RESULTS In the model group， the placental tissues of rats were hyperemia and dilatation， with fewer and irregular blood vessels； severe stromal edema，inflammatory cell infiltration and iron-choledrin depositionwere observed. Compared with model group， the fetal survival rates， serum levels of β-HCG and P， the expressions of PCNA and HB-EGF mRNA and proteins in the placenta and decidua tissue of soybean isoflavone groups increased significantly （P＜ 0.05）， while pathological changes were improved significantly； cell apoptosis index in the placenta and decidua tissue， the expressions of Fas， FasL mRNA and proteins in the placenta and Fas mRNA and protein in the decidua tissue decreased significantly （P＜0.05）. The effect of soybean isoflavones was dose-dependent （P＜0.05）. CONCLUSIONS Soybean isoflavone has protective effect on threatened miscarriage， the mechanism of which is related to down-regulating the expressions of Fas and FasL mRNA and protein at the maternal-fetal interface， and up-regulating the expressions of mRNA and protein of PCNA and HB- EGF.

Comparison of maternal complications between fresh and frozen embryo transfer during gestation.

Objective: Maternal complications in infertile women undergoing in vitro fertilization are an important discussion, and patients should be informed about these complications depending on the method of embryo transfer. In this study, maternal complications during gestation were compared between frozen and fresh embryo transfer in infertile women who underwent in vitro fertilization at Shariati Hospital from 2018 to 2021. Materials and Methods: This study was a retrospective cohort study, and patient data were collected using archive files. From 396 in vitro fertilization patients, 302 were in the frozen embryo transfer group and 94 were in the fresh embryo transfer group. Patients in both groups were similar in terms of the number of transferred embryos and age (p>0.05). Data regarding threatened miscarriage, early miscarriage, placenta previa occurrence, gestational hypertension, preterm birth, gestational diabetes, and pre-eclampsia were gathered and compared between the two groups. Results: The rates of threatened miscarriage, placenta previa, gestational hypertension, gestational diabetes, preterm birth, and pre-eclampsia were not significantly different between the fresh and frozen embryo transfer groups (p>0.05). However, the early miscarriage rate in the fresh embryo transfer group was significantly higher (34% vs. 16.2%, p<0.001). Conclusion: According to the results of this study, maternal complications, except early miscarriage, were not different between fresh and frozen embryo transfer. However, frozen embryo transfer is safer in terms of the early miscarriage rate.

Threatened miscarriage and recurrent miscarriage: Expert opinions on progesterone therapy and treatment challenges.

It is crucial to gain a better understanding of threatened and recurrent miscarriages, including the existing knowledge and unknowns, as well as to discuss medical approaches and assess the situation. These issues are outstanding problems, causing significant physical and emotional burdens on women and their families, not only in Turkey but also worldwide. This article aims to explore the topic of miscarriages, including the implications, challenges, and potential therapeutic approaches in Turkey. Nineteen statements were presented to 6 Turkish perinatologists and obstetricians and gynecologists to evaluate the management of threatened and recurrent miscarriage and to compare the results with literature recommendations in an expert opinion meeting. Turkish perinatologists and obstetricians & gynecologists provided their responses using a 5-point Likert scale and discussed every statement. Progesterone use, particularly oral dydrogesterone, was supported by most of the experts. Opinions varied on the preference for dydrogesterone in recurrent miscarriage treatment. Experts unanimously agreed on the efficacy and safety of dydrogesterone and its recommendation in guidelines for threatened and recurrent miscarriage. Regarding progesterone therapy, vaginal progesterone was not associated with an increased rate of live births. Side effects of vaginal and oral micronized progesterone were acknowledged, and compliance with oral progesterone treatment was generally agreed upon. Dydrogesterone activity and effectiveness in threatened miscarriage received positive responses, while opinions on its effectiveness in recurrent miscarriage were divided. The loading dose of dydrogesterone and the practice of checking blood progesterone levels had different opinions among experts.This manuscript provides valuable insights in the management of threatened and recurrent miscarriages, highlighting the role of progesterone therapy, specifically dydrogesterone, and the need for adherence to relevant guidelines. Further research and a national Turkish guideline are warranted to address areas of uncertainty and optimize the management of these conditions.

Efficacy and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage: a systematic review and meta-analysis.

Background: Despite some progress has been made in the pathogenesis and treatment of threatened miscarriage (TM), conventional treatment remains suboptimal. Thus, complementary medicine gradually become a new treatment option for treating threatened miscarriage. Gushen Antai Pills (GAP), a classic prescription of Traditional Chinese medicine (TCM), has became a popular complementary therapy to conventional western medicine (dydrogesterone) in treating threatened miscarriage in recent years. However, a systematic summary and analysis for its therapeutic effects is lacking. This meta-analysis aimed to systematically evaluate the effectiveness and safety of Gushen Antai Pills combined with dydrogesterone in the treatment of threatened miscarriage. Methods: A systematic search across seven electronic databases was conducted from inception to 17 September 2022. Studies were included if they were randomized controlled trials (RCTs) evaluating the effect of integrating Gushen Antai Pills and dydrogesterone in patients with threatened miscarriage, and reported the outcomes of interest. All statistical analyses were conducted using the Revman5.3 and Stata 13 software. The GRADE system was used to evaluate the quality of evidence. Results: Ten eligible randomized controlled trials involving 950 participants were contained in this meta-analysis. The pooled analysis showed that Gushen Antai Pills combined with dydrogesterone can significantly reduce the incidence of early pregnancy loss (RR: 0.29; 95% CI: 0.19-0.42; p < 0.00001) and alleviate clinical symptoms (RR: 1.39; 95% CI: 1.22-1.59; p < 0.00001), compared with treatment of dydrogesterone alone. Also, meta-analysis indicated that integrating Gushen Antai Pills and dydrogesterone is more effective than using dydrogesterone alone in improving hormone levels (serum levels of progesterone, ß-HCG and estradiol) for women with threatened miscarriage (all p < 0.00001). Meanwhile, the combined effects with significant heterogeneity also showed favorable consistency in the sensitivity analyses, indicating a good stability of present results. Moreover, no significant differences between Gushen Antai Pills combined with dydrogesterone and control group on adverse events was identified. The overall GRADE qualities were low to moderate. Conclusion: The overall available evidence suggested that Gushen Antai Pills combined with dydrogesterone had significant effects in improving pregnancy success rate, clinical symptoms and hormone levels for women with threatened miscarriage, with considerable safety and reliability. However, due to the partial heterogeneity, suboptimal quality and high risk of bias of some included studies, further rigorously designed randomized controlled trials are required. Systematic Review Registration: identifier https://INPLASY2022120035, https://inplasy.com/inplasy-2022-12-0035/.

The Utility of Transvaginal Ultrasound After Intrauterine Pregnancy Identification on Transabdominal Ultrasound in Emergency Department Patients.

Introduction: Ultrasonography has an important role in the evaluation of Emergency Department (ED) patients presenting with early pregnancy complaints. Both transabdominal (TAUS) and transvaginal ultrasound (TVUS) can be utilized. While TVUS generally allows for greater detail, it is unclear how much added benefit exists in performing TVUS once an intrauterine pregnancy (IUP) has been identified on TAUS. Methods: This was a retrospective study utilizing Radiology Department ultrasound examinations obtained in first trimester pregnancy ED patients during a consecutive four month period in 2019. Studies wherein both TAUS and TVUS were both performed were included. Two ED physicians with specialized training in point of care ultrasound reviewed only the TAUS images from these studies. Their findings were compared to the Radiologist interpretation, which was inclusive of both TAUS and TVUS components of the study. Results: 108 studies met inclusion criteria. Amongst these, 82 had IUP's identified on the radiologist report. 69 studies had an IUP identified by ED physician review of the TAUS images, with 1 false positive. Each case of intrauterine fetal demise (IUFD) was identified on ED physician review of TAUS. Two ectopic pregnancies were present, neither of which was mistaken for IUP on ED physician TAUS review. There were 15 studies with subchorionic hemorrhage and 3 studies with an ovarian cyst noted on the radiologist report. Conclusion: Following the identification of an IUP on TAUS, the added diagnostic value of TVUS amongst this cohort of ED patients was low. Given the added time and cost of TVUS, selective instead of routine usage should be encouraged.

Zishen yutai pill as an adjuvant therapy in threatened Miscarriage:A meta-analysis of 23 randomized controlled trials.

Objective: The purpose of this study was to evaluate the efficacy and safety of Zishen Yutai Pill combined with western medicine for the treatment of women with threatened miscarriage during the first trimester of pregnancy. Methods: Randomized controlled trials published before the end of Apr 1, 2023 on Zishen Yutai Pill and threatened miscarriage were systematically retrieved from China National Knowledge Infrastructure, Wanfang, Sinomed, VIP, PubMed, EMBASE, Web of Science and the Cochrane Library. The international clinical trial registration platform and the Chinese clinical trial registration platform of clinical trials was searched from their inception until Apr 1, 2023. Meta analysis of random effect model was used to combine the research data. Chi-squared test and I2 statistics were used for heterogeneity test. Results: Twenty-three trials (enrolling 2411 participants) were included in the review. Zishen Yutai pill combined with western medicine therapy showed significant improvement on human chorionic gonadotropin [MD 19.33 IU/ml, 95% CI (15.84, 22.81)], the total effective rate [RR 1.19, 95% CI (1.15-1.23)], progesterone [MD 7.14 ng/ml, 95% CI (6.14, 8.13)], estradiol [MD 33.69 pg/ml, 95% CI (27.42, 39.96)], duration of abdominal pain [MD -2.36 d, 95% CI (- 3.54, - 1.18)], duration of vaginal bleeding [MD -1.94 d, 95% CI (- 2.93, - 0.94)], and fibrinogen [MD -0.34 g/L, 95% CI (- 0.57, - 0.11)]. There was no significant difference in hematocrit [MD 0.68%, 95% CI (- 0.08, 1.44)] between the experimental and the control group. Zishen Yutai Pill may improve the clinical symptoms in women with threatened miscarriage, such as human chorionic gonadotropin the total effective rate, progesterone, estradiol, duration of abdominal pain, duration of vaginal bleeding, and fibrinogen. Especially for progesterone, the effect of treatment ≦2 weeks is significantly better than treatment of >2 weeks. For estradiol, the effect of treatment >2 weeks is significantly better than treatment of ≦ 2 weeks. Conclusion: Zishen Yutai Pill, as a complementary therapy, significantly improved human chorionic gonadotropin, the total effective rate, progesterone, estradiol, abdominal pain, vaginal bleeding, and fibrinogen in patients with threatened miscarriage in first-trimester pregnancy. However, the systematic review has some limitations, such as degraded information quality, no blinding of patients or doctors, etc. Due to the small sample size and low quality of research, it needs to be further confirmed by large sample and high-quality randomized controlled trials, such as blinding of patients, doctors and outcome assessment should be complemented, clinical follow-up, live birth rate, fetal growth should be supplemented. Systematic review registration: INPLASY202320039.

How endocervicoscopy can impact obstetric outcomes in women undergoing LEEP for CIN2 + : a retrospective cohort analysis.

PURPOSE: To assess the impact of preoperative endocervicoscopy on obstetric outcomes and complications in women undergoing LEEP for CIN2 + . METHODS: This was a retrospective cohort study carried out between October 2012 and April 2018. All women had undergone cervical length measurement at T0 (before LEEP), T1 (6 months after LEEP), and T2 (at 20 weeks of pregnancy) through transvaginal ultrasound examination after LEEP for CIN2 + . A total of 528 patients fulfilled our inclusion criteria and contributed to the final analysis: 288 had undergone endocervicoscopy before the excisional procedure (Group A), while the remaining 240 (Group B) did not. RESULTS: Patients who did not undergo endocervicoscopy showed a greater amount of tissue excised at LEEP compared to those of Group A (6.7% vs 31.9% in Group A and B, p < 0.01, respectively). A statistically relevant difference was detected in the lesion margins involvement: negative in 93.8% in Group A compared to 65.6% in Group B. The cervicometry before the treatment resulted in similar between the two groups, while a statistically significant difference was noted after 6 months (37.5 ± 2.9 mm in Group A vs 35.1 ± 3.8 mm in Group B, p < 0.01) and at 20th week pregnancy (36.9 ± 5.3 mm in Group A vs 33.5 ± 5.6 mm in Group B, p < 0.01). The number of pregnancies after LEEP as well as the difference in the elapsed time (in months) did not result in a statistical significance between the two groups. The threatened preterm labor (TPL) and the threatened miscarriage showed a statistically significant difference in incidence between the two groups (4,2% and 4.2% in Group A vs 15.3% and 25% in Group B, p < 0.01, respectively). CONCLUSION: Endocervicoscopy reduces the size of the LEEP sample and in particular its depth, saving healthy cervical tissue, and guarantees the total eradication of the lesion as the resection margins are negative in almost all cases, allowing for a reduction of the rate of TPL and threatened miscarriage in women with CIN2 + , especially with Type 2 or 3 cervical squamocolumnar junction (SCJ).

The effects of dydrogesterone treatment on first-trimester aneuploidy screening markers and nuchal translucency in women with threatened miscarriage.

Objective: To evaluate the effects of dydrogesterone treatment on first-trimester aneuploidy screening markers and nuchal translucency (NT) in women with threatened miscarriage. Materials and Methods: This study is an prospective case-control study. One hundred seven pregnant women who applied for the first-trimester screening test at 11-14th weeks of gestation were included in the study. The study group consisted of 53 pregnant women using oral dydrogesterone due to the threat of miscarriage for at least 2 weeks and without vaginal bleeding for the last 72 h at the time of enrollment. The control group was composed of 54 healty pregnant women. Fetal Crown-rump length (CRL), NT, pregnancy-associated plasma protein-A (PAP-A) level, and free beta-human chorionic gonadotropin (free B-hCG) levels of the patients were measured. Results: One hundred seven patients included in the study, 54 (50.46%) were in the control group, and 53 (49.54%) were in the study group using dydrogesterone. Age, body mass index, gravida, parity and abortion numbers, gestational weeks, and CRL values of the two groups were congruent. In the comparison-free B-hCG, PAPP-A and NT values of both groups, no statistically significant difference was found between the two groups in terms of first-trimester test results and NT (p<0.05). Conclusion: The use of dydrogesterone in first-trimester pregnancies does not affect first-trimester screening tests and nuchal translucency.

Acupuncture Treatment for Threatened Abortion.

Background: Threatened abortion, also known as threatened miscarriage, is a common complication in pregnant women; it seriously harms their physical and mental health. However, there are only a few reports on acupuncture treatment to address threatened abortion. Case: A woman had a threatened abortion. She experienced vaginal bleeding and had an intrauterine hematoma after embryo transfer. She declined medication use because of concerns about the adverse effects to the embryo. Therefore, acupuncture treatment was performed to relieve her pain and save the fetus. Results: After the 4th treatment, her vaginal bleeding stopped, and her uterine effusion was reduced to 27 × 22 mm. After the 11th treatment, the uterine effusion decreased even more-to 40 × 7 mm-and disappeared completely after the 16th treatment. No adverse events occurred during her treatment, and her bleeding and uterine effusion did not recur. The fetus developed normally, and the child was born. This child is currently healthy and growing. Conclusions: By stimulating the body's acupoints, acupuncture can be used to adjust the Qi and Blood, and consolidate Extraordinary Vessels, mainly in Chong and Ren, to prevent miscarriage. This case report provided information about the treatment of a threatened abortion and illustrated how acupuncture was be used to stop a threatened abortion. This report can be utilized to support high-quality randomized controlled trials. Given that there is a lack of standardized and safe procedures for treating threatened abortion by using acupuncture, this research is needed.

Chinese herbal medicine for threatened miscarriage: An updated systematic review and meta-analysis.

Objective: To conduct an updated systematic review and meta-analysis on the efficacy and safety of Chinese herbal medicine (CHM) for threatened miscarriage. Data Sources: Electronic databases were searched from inception to 30 June 2022. Study Eligibility Criteria: Only randomized controlled trials (RCTs) that assessed the efficacy and safety of CHM or combined CHM and Western medicine (CHM-WM) and compared with other treatments for threatened miscarriage were included for analysis. Methods: Three review authors independently evaluated included studies, assessed the risk of bias and extracted data for meta-analysis (continuation of pregnancy after 28 gestational weeks, continuation of pregnancy after treatment, preterm birth, adverse maternal outcomes, neonatal death, TCM syndrome severity, ß-hCG levels after treatment), sensitivity analysis (ß-hCG level) and subgroup analysis (TCM syndrome severity, ß-hCG level). The risk ratio and 95% confidence interval were calculated by RevMan. Certainty of the evidence was assessed according to GRADE. Results: Overall, 57 RCTs involving 5,881 patients met the inclusion criteria. Compared with WM alone, CHM alone showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (Risk Ratio (RR) 1.11; 95% CI 1.02 to 1.21; n = 1; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.30; 95% CI 1.21 to 1.38; n = 10; moderate quality of evidence), higher ß-hCG level (Standardized Mean Difference (SMD) 6.88; 95% CI 1.74 to 12.03; n = 4) and lower Traditional Chinese medicine (TCM) syndrome severity (SMD -2.94; 95% CI -4.27 to -1.61; n = 2). Compared with WM alone, combined CHM-WM showed significant higher incidence of continuation of pregnancy after 28 gestational weeks (RR 1.21; 95% CI 1.16 to 1.27; n = 15; moderate quality of evidence), continuation of pregnancy after treatment (RR 1.19; 95% CI 1.16 to 1.23; n = 41; moderate quality of evidence), higher ß-hCG level (SMD 2.27; 95% CI 1.72 to 2.83; n = 37) and lower TCM syndrome severity (SMD -1.74; 95% CI -2.21 to -1.27; n = 15). No significant differences in reducing the adverse maternal outcomes and neonatal death were found in combined CHM-WM compared with WM alone (RR 0.97; 95% CI 0.62 to 1.52; n = 8; RR 0.39; 95% CI 0.12 to 1.21; n = 2). Conclusion: Current evidence supported CHM could be a potential treatment for threatened miscarriage. However, results should be interpreted with caution considering the low to moderate quality of the available evidence. Systematic Review Registration: [https://inplasy.com/inplasy-2022-6-0107/], identifier [INPLASY20220107].

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

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

Defects in protective cytokine profiles in spontaneous miscarriage in the first trimester.

OBJECTIVE: To study differences in cytokine expression profiles between women with ongoing pregnancy and those experiencing spontaneous miscarriage, among women who presented with threatened miscarriage before week 16 of gestation. DESIGN: Prospective cohort study. SETTING: Academic hospital. PATIENT(S): In this prospective cohort study, 155 pregnant women, comprising normal pregnant women recruited from antenatal clinics (n = 97) and women with threatened miscarriage recruited from an emergency walk-in clinic (n = 58). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Sixty-five serum cytokines quantified using multiplex immunoassay correlated with miscarriage outcomes. RESULT(S): Among women presenting with threatened miscarriage, those who eventually miscarried had significantly lower levels of interleukin (IL)-2, IL-12p70, IL-17A, B-cell-activating factor, B lymphocyte chemoattractant, basic nerve growth factor, interferon-γ, tumor necrosis factor-related apoptosis-inducing ligand, thymic stromal lymphopoietin, and tumor necrosis factor-α and higher levels of vascular endothelial growth factor A, IL-21, and stromal cell-derived factor 1α than those with ongoing pregnancy. Comparisons between normal pregnancies and women with threatened miscarriage who eventually miscarried revealed significant differences across 7 cytokines: B-cell-activating factor; B lymphocyte chemoattractant; basic nerve growth factor; IL-17A; fractalkine/CX3CL1; vascular endothelial growth factor A; and CCL22. Vascular endothelial growth factor A exhibited a negative correlation with the progesterone level (r = -0.270). The cluster of significant cytokines alludes to T cell proliferation, B-cell proliferation, natural killer cell-mediated cytotoxicity, and apoptosis as important pathways that determine pregnancy outcomes. Bioinformatic analysis further revealed alteration of the suppressor of cytokine signaling proteins family of Janus kinase-signal transducer and activator of transcription signaling axis by cytokines as a plausible key molecular mechanism in spontaneous miscarriage. CONCLUSION(S): This study demonstrates that the regulated balance between the proinflammatory and anti-inflammatory pathways is crucial to maintaining pregnancy. A better understanding of the cytokines associated with immunomodulatory effects may lead to novel targets for the prediction and treatment of spontaneous miscarriage.