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).

Construction of machine learning tools to predict threatened miscarriage in the first trimester based on AEA, progesterone and ß-hCG in China: a multicentre, observational, case-control study.

BACKGROUND: Endocannabinoid anandamide (AEA), progesterone (P4) and ß-human chorionic gonadotrophin (ß-hCG) are associated with the threatened miscarriage in the early stage. However, no study has investigated whether combing these three hormones could predict threatened miscarriage. Thus, we aim to establish machine learning models utilizing these three hormones to predict threatened miscarriage risk. METHODS: This is a multicentre, observational, case-control study involving 215 pregnant women. We recruited 119 normal pregnant women and 96 threatened miscarriage pregnant women including 58 women with ongoing pregnancy and 38 women with inevitable miscarriage. P4 and ß-hCG levels were detected by chemiluminescence immunoassay assay. The level of AEA was tested by ultra-high-performance liquid chromatography-tandem mass spectrometry. Six predictive machine learning models were established and evaluated by the confusion matrix, area under the receiver operating characteristic (ROC) curve (AUC), accuracy and precision. RESULTS: The median concentration of AEA was significantly lower in the healthy pregnant women group than that in the threatened miscarriage group, while the median concentration of P4 was significantly higher in the normal pregnancy group than that in the threatened miscarriage group. Only the median level of P4 was significantly lower in the inevitable miscarriage group than that in the ongoing pregnancy group. Moreover, AEA is strongly positively correlated with threatened miscarriage, while P4 is negatively correlated with both threatened miscarriage and inevitable miscarriage. Interestingly, AEA and P4 are negatively correlated with each other. Among six models, logistic regression (LR), support vector machine (SVM) and multilayer perceptron (MLP) models obtained the AUC values of 0.75, 0.70 and 0.70, respectively; and their accuracy and precision were all above 0.60. Among these three models, the LR model showed the highest accuracy (0.65) and precision (0.70) to predict threatened miscarriage. CONCLUSIONS: The LR model showed the highest overall predictive power, thus machine learning combined with the level of AEA, P4 and ß-hCG might be a new approach to predict the threatened miscarriage risk in the near feature.

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

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

Proceso de enfermería a embarazada con infección de vías urinarias y amenaza de aborto / A Nursing Process for a Pregnant Woman with Urinary Tract Infection and Threatened Miscarriage

Introducción: La infección de vías urinarias es recurrente en el embarazo y generadora de complicaciones. Objetivo: Presentar un plan de cuidados enfermero a una mujer con diagnóstico infección de vías urinarias y amenaza de aborto Métodos: Caso clínico de paciente admitida en unidad de Ginecología y Obstetricia del Hospital General de Teziutlán, Puebla, México, durante 2019. Siguiendo la lógica del proceso de enfermería, la valoración se fundamentó en los patrones funcionales de salud de Marjory Gordon. Fueron utilizadas las terminologías normalizadas de enfermería: Diagnósticos (NANDA.int). Resultados (NOC) e Intervenciones (NIC). Resultados: Se identificaron cuatro diagnósticos de enfermería: deterioro de la eliminación urinaria, gestión ineficaz de la propia salud, disposición para mejorar la nutrición y riesgo de alteración de la díada materno/fetal, este último diagnóstico principal. Además, un Resultado NOC (Conocimiento: Control de Infección), cuatro indicadores y la escala de nunca a siempre demostrado; cuatro Intervenciones NIC, con 19 actividades. La evaluación transitó desde 12 (puntuación inicial) a 19 (puntuación final), de 20 como puntuación diana. Conclusión: La integración de las taxonomías NANDA, NIC, NOC y los patrones funcionales de salud de Marjory Gordon permitió diseñar el plan de cuidado de la embarazada, fueron articulados diagnósticos, resultados e intervenciones de enfermería que favorecieron la relación enfermera-paciente-contexto sociocultural, para llevar el cuidado hasta una concepción sistémica que permita el seguimiento y control de la embarazada(AU)

Introduction: Urinary tract infection is recurrent in pregnancy and causes complications. Objective: To present a nursing care plan provided to a woman with a diagnosis of urinary tract infection and threatened miscarriage. Methods: Clinical case of a patient admitted to the gynecology and obstetrics unit of General Hospital of Teziutlán (Puebla, Mexico) during 2019. Following the logic of the nursing process, the assessment was based on Marjory Gordon's functional health patterns. The standard nursing terminologies were used: diagnostics (NANDA-I), outcomes (NOC) and interventions (NIC). Results: Four nursing diagnoses were identified: deterioration of urinary elimination, ineffective self-health management, willingness to improve nutrition, and risk for alterations in maternal-fetal dyad, the latter being the main diagnosis. In addition, a NOC outcome (knowledge: infection control), four indicators and the never-to-always scale upon demonstration, as well as four NIC interventions, with nineteen activities, were obtained. Evaluation ranged from twelve (initial score) to nineteen (final score), with twenty as target score. Conclusion: The integration of the NANDA, NIC and NOC taxonomies together with the Marjory Gordon's functional health patterns allowed the design of the pregnant woman's care plan, with an articulation between nursing diagnoses, outcomes and interventions, which favored the nurse-patient-sociocultural context relationship, up to considering care based on a systemic conception that allows monitoring and control of the pregnant woman(AU)

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.

New thoughts in exploring the pathogenesis, diagnosis, and treatment of threatened abortion.

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.

First Trimester Bleeding: Evaluation and Management.

Approximately one-fourth of pregnant women will experience bleeding in the first trimester. The differential diagnosis includes threatened abortion, early pregnancy loss, and ectopic pregnancy. Pain and heavy bleeding are associated with an increased risk of early pregnancy loss. Treatment of threatened abortion is expectant management. Bed rest does not improve outcomes, and there is insufficient evidence supporting the use of progestins. Trends in quantitative ß subunit of human chorionic gonadotropin (ß-hCG) levels provide useful information when distinguishing normal from abnormal early pregnancy. The discriminatory level (1,500 to 3,000 mIU per mL) is the ß-hCG level above which an intrauterine pregnancy should be visible on transvaginal ultrasonography. Failure to detect an intrauterine pregnancy, combined with ß-hCG levels higher than the discriminatory level, should raise concern for early pregnancy loss or ectopic pregnancy. Ultrasound findings diagnostic of early pregnancy loss include a mean gestational sac diameter of 25 mm or greater with no embryo and no fetal cardiac activity when the crown-rump length is 7 mm or more. Treatment options for early pregnancy loss include expectant management, medical management with mifepristone and misoprostol, or uterine aspiration. The incidence of ectopic pregnancy is 1% to 2% in the United States and accounts for 6% of all maternal deaths. Established criteria should be used to determine treatment options for ectopic pregnancy, including expectant management, medical management with methotrexate, or surgical intervention.

Does progesterone therapy increase nuchal translucency in women with threatened miscarriage?

OBJECTIVES: The effect of exogenous progesterone on fetal nuchal translucency (NT) has been proposed recently. In this study, we aimed to compare the thickness of NT of patients receiving and not receiving progesterone for threatened miscarriage. MATERIAL AND METHODS: This study was designed as a retrospective comparative study. Ninety five women treated with progesterone constituted the study group whereas 97 women who were not treated with progesterone constituted the control group. An ultrasonographic examination was performed on all of the women to measure NT. All patients were treated with oral micronized progesterone in the study group. The main parameters recorded for each woman were; age, body mass index (BMI), obstetrical characteristics, and gestational age at first examination, treatment duration of progesterone therapy, and results of combined and triple tests. RESULTS: A total of 192 pregnant women with threatened miscarriage were included in this study. The mean NT thickness was statistically significantly higher in the study group (p < 0.001), and mean serum level of human chorionic gonadotropin (hCG) was also higher in this group (p < 0.05). There was no statistically significant difference between groups in terms of age, BMI, and gestational age at first examination. ROC curve analysis demonstrated that only increased NT (area under the curve: 0.634, p = 0.005, 95% CI: 0.541-0.727) was a discriminative factor for women receiving progesterone for threatened miscarriage. Also there was a positive correlation between NT and treatment duration (r = 0.269; p < 0.001). CONCLUSIONS: We think that oral progesterone therapy may increase NT depending on treatment duration without causing abnormal prenatal screening test results.

Role of serum biomarkers in the prediction of outcome in women with threatened miscarriage: a systematic review and diagnostic accuracy meta-analysis.

BACKGROUND: Threatened miscarriage affects one in five women and is associated with significant emotional distress. The uncertainty around the prognosis of threatened miscarriage makes it equally challenging to the healthcare professionals. Various biochemical markers have been investigated in the past to predict the outcome of threatened miscarriage; however, the results have been conflicting. Therefore, we have conducted a systematic review and meta-analysis to determine the diagnostic accuracy of biochemical markers in predicting the outcome in women presenting with threatened miscarriage. METHODS: This is a systematic review and meta-analysis of prospective studies that investigated biochemical markers to determine outcomes for women with threatened miscarriage at 5-23 weeks gestational age. Electronic databases were searched up to June 2015 and study quality assessment was performed using QUADAS-2 (Quality Assessment for Diagnostic Accuracy Studies-2: A Revised Tool) for evaluating the diagnostic accuracy studies. Statistical analysis was performed using the Cochrane systematic review software. RESULTS: A total of 19 studies were included in the qualitative data synthesis of which 15 (including 1263 women) were eligible for the meta-analysis. The review highlights the role of biochemical markers serum progesterone, hCG, pregnancy associated plasma protein A, estradiol and cancer antigen 125 (CA 125) in the prediction of outcome in women with threatened miscarriage. Interestingly, serum CA 125 appears to be the most promising marker (n = 648 women in seven studies), whereas serum progesterone and hCG are less useful once fetal viability is established. The summary receiver operating characteristics for CA 125 showed a sensitivity of 90% (95% confidence interval (CI) 83-94%), specificity of 88% (95% CI 79-93%), positive likelihood ratio of 7.86 (95% CI 4.23-14.60) and negative likelihood ratio of 0.10 (95% CI 0.06-0.20). The inverse of negative likelihood ratio was 9.31 (95% CI 5-17.1) indicating that a negative test is likely to identify those who are likely to continue with the pregnancy. Serum estradiol was the next best marker with a sensitivity of 45% (95% CI 6-90%), a specificity of 87% (95% CI 81-92%), a positive likelihood ratio of 3.72 (95% CI 1.01-13.71) and a negative likelihood ratio of 0.62 (95% CI 0.20-1.84). CONCLUSIONS: In women with threatened miscarriage, serum CA 125 has high predictive value in identifying pregnancies that are 'likely to continue', whereas the most commonly used biomarkers of serum hCG and progesterone are not useful in predicting outcome of a pregnancy with a viable fetus. Other markers such as inhibin A and a combination of markers need to be investigated to hopefully improve the prediction of outcome in women with threatened miscarriage.

Ameaça de aborto: conduta baseada em evidências / Threatened miscarriage: conduct based on evidences

A ameaça de aborto é definida como sangramento vaginal, geralmente indolor, que ocorre na primeira metade da gravidez com concepto vivo sem dilatação cervical. Muitas intervenções são utilizadas para a ameaça de aborto espontâneo. Quando uma causa específica é identificada, o tratamento direcionado pode reduzir taxas de abortamento. No entanto, na maioria dos casos, a fisiopatologia permanece desconhecida. Intervenções inespecíficas como repouso no leito e ausência de relações sexuais, apesar de comumente aconselhadas pelos médicos, não têm comprovação de benefício. A didrogesterona, um derivado progestínico, parece reduzir o risco de abortamento. Esta revisão mostra a qualidade das evidências científicas e o grau de recomendação das várias condutas para o tratamento da ameaça de aborto, concluindo que ainda é necessário realizar outros ensaios clínicos maiores, placebo-controlados e randomizados sobre o tratamento da ameaça de aborto para definir a eficácia da maioria das intervenções

Threatened miscarriage is defined as a vaginal bleeding, usually painless, which occurs in the first half of viable pregnancy without cervical dilatation. Many interventions are used for threatened and recurrent miscarriage. When a specific cause is identified, directed treatment may reduce miscarriage rates. However, in the majority of cases, the pathophysiology remains unknown. Unspecific interventions, as bed rest and avoidance of sexual intercourse, though commonly advised, are of no proven benefit. Dydrogesterone, a progesterone derivative, may further reduce miscarriage rates. This review shows the scientific evidence and classification quality of several interventions for the treatment of threatened miscarriage. Larger, randomized and controlled trials on the treatment of threatened miscarriage are needed to support the majority of the interventions

Bioactive to immunoreactive ratio of circulating human chorionic gonadotropin as possible evaluation for the prognosis of threatened abortion.

OBJECTIVE: In an effort to evaluate the prognosis of threatened abortion, we established the ratio of serum human chorionic gonadotropin (hCG), as measured by bioassay or radioimmunoassay techniques, of samples from patients with threatened abortion or normal pregnancy. STUDY DESIGN: Peripheral blood samples from patients in their first trimester of pregnancy with threatened abortion (n=24), or normal pregnancy (n=12), were assayed for progesterone (RIA), and for immunoactive (DELFIA) and bioactive (mouse Leydig cell testosterone production assay) hCG. RESULTS: Serum progesterone was not statistically different between the threatened-continuing and the threatened-miscarried groups. The ratio of hCG bioactive/hCG immunoactive (B/I) was significantly lower for the patients of the threatened group that experienced abortion. The B/I ratio for the control and threatened-continuing patients was similar. CONCLUSION: The hCG bioactive/hCG immunoactive ratio could be a good indicator of the prognosis of threatened abortion.

[Biochemical and sonographic values in early pregnancy in women with a history of early spontaneous abortion]. / Vrednosti biohemijskih i sonografskih parametara u ranoj trudnoci kod zena sa spontanim pobacajima u ranijoj anamnezi.

INTRODUCTION: The aim of this study was to examine interconnections between changes in serum levels of biochemical parameters during pregnancy and sonographic parameters relevant for evaluation of early pregnancy. MATERIAL AND METHODS: We analyzed serum levels of human chorionic gonadotropin (hCG), estradiol (E2), progesterone (PRG) and prolactin (PRL) using ELISA method, in cases of complicated pregnancies with symptoms of imminent miscarriage, and in patients with uncomplicated pregnancies. We evaluated their impact on mean gestational sac diameter (MSD), crown-rump length (CRL), inner diameter of the vitelline sac (SV), trophoblast (Trf) thickness and embryonic heart rate (STP). All results were correlated using Pearson's test and regression. RESULTS: Changes in biochemical parameters of pregnancy correlate significantly with dimensions of analyzed sonographic parameters. DISCUSSION: Levels of chorionic gonadrotropin affect production of ovarian and placental steroidogenesis. Interrelations were also discussed. CONCLUSION: Changes in biochemical values of pregnancy hormones affect dimensions of analyzed sonographic parameters. During uncomplicated pregnancy, levels of chorionic gonadotropin, progesterone and estradiol affect mean gestation-sac diameter, embryo length, depth of trophoblast invasion and formation and function of vitelline sac, and thus they alter the embryonic heart rate.

Prostacyclin and hormone levels in patients with symptoms of miscarriage and infection.

During pregnancy, acsending infection into the uterus, is followed by local increase of cyclooxygenase-2 (COX-2) activity, and consequently elevated prostaglandin production. Subclinical infections of fetal amniotic membranes are well known to cause preterm delivery. Spreading of infection from vagina and cervix into uterine cavity, can be tragic for the fetus. The aim of this study was to reveal wether lower genital tract infections are associated with symptoms of threatened miscarriage. Our investigation included 140 patients with symptoms of threatened miscarriage and 70 patients with uncomplicated pregnancies. Infections were detected by vaginal or cervical smears as well as tests for Chlamydial infection. Levels of prostacyclin, main prostaglandin product during pregnancy, were evaluated via its stable metabololite, 6-keto-PGF1-alpha. Both prostaglandin levels and hormones were determined by ELISA method. We found that serum values of prostacyclin were elevated, while levels of estradiol, progesterone and prolactin were significantly lower in patients with lower genital tract infections. Increased prostacyclin levels in pregnancies complicated by lower genital tract infections are caused by stimulation of COX/2 enzyme, due to elevated production of various cytokines which are possibly a compensatory mechanism resolving problems caused by bacterial endotoxines.

[Levels of essential elements in pubic hair of women with threatened abortion and in full-term pregnancy]. / Metale esencjalne we wlosach lonowych u kobiet z poronieniem zagrazajacym i w ciazy donoszonej.

Concentrations of iron, zinc and copper were determined in public hair of women with threatened abortion and in full-term pregnancy. The aim of the studies was to find differences between the levels of studied elements in public hair of women with threatened abortion and in full-term pregnancy and to test whether parity, place of residence and smoking influence the measured levels. A study population consisted of 101 women aged 18-41 years. Atomic absorption spectrophotometry was the method employed to determine the concentrations of the studied elements. The levels of copper were elevated in smokers in full-term pregnancy in comparison to nonsmokers.