Comparison of VEGF-A levels in women with threatened abortion, early pregnancy loss and uncomplicated healthy pregnancies.

INTRODUCTION: To estimate the possible role of VEGF-A in predicting poor early pregnancy outcomes including threatened abortion and early pregnancy loss. METHODS: We conducted a prospective case-control study with three groups of pregnant women diagnosed with threatened abortion, early pregnancy loss, and uncomplicated healthy pregnancies between 01 March 2023 and 15 March 2023. Maternal serum VEGF-A concentration was measured using the Sandwich-ELISA method in accordance to the commercial kit's instructions. There were 30 patients in each 3 group and the gestational age of the patients was between 6 and 14 weeks. The Kruskal-Wallis test was performed for comparing the median values between the groups. Mann-Whitney U test was conducted for pairwise comparisons. RESULTS: VEGF-A levels were compared between 3 groups and a statistically significant difference was found (p = 0.007). There was a moderately significant correlation between VEGF-A levels and poor early pregnancy outcomes. For poor early pregnancy outcomes, the area under the curve (AUC) was 0.75 (95% CI: 0.64-0.85). The best balance of sensitivity/specificity in ROC curves was 0.60 (63.3% sensitivity, 74.3% specificity). DISCUSSION: In conclusion, this study pointed out the increased VEGF concentrations in pregnant women with threatened miscarriage and early pregnancy loss. VEGF-A may be a potential biomarker for the indication of poor early pregnancy outcomes.

Role of the systemic immune-inflammation index in threatened abortion patients and predicting of abortion.

PURPOSE: Our study aimed to compare the systemic immune inflammation index (SII), one of the hematological inflammation parameters, between pregnant women diagnosed with threatened abortion (TA) and healthy pregnant women, and to evaluate the prediction of abortion in pregnant women with TA. METHODS: This retrospective study compared 150 patients with TA group and 150 age- and gestational week-matched healthy pregnant women (control group). Complete blood count parameters were assessed. SII, white blood cells (WBC), neutrophil to lymphocyte ratio (NLR), red cell distribution width (RDW), plateletcrit (PCT), platelet distribution width and monocyte to lymphocyte ratio (MLR) values were calculated. The SII value was calculated as follows: platelet count × (neutrophil/lymphocyte). RESULTS: SII, NLR, MLR, WBC, RDW, and PCT values were significantly higher in the TA group compared to the control group (923 ± 683 vs. 579 ± 364 [p < 0.001], 3.3 ± 2.0 vs. 2.1 ± 1.1 [p < 0.001], 0.3 ± 0.1 vs. 0.2 ± 0.2 [p < 0.001], 9.84 ± 2.87 vs. 8.6 ± 1.6 [p < 0.001], 13.9 ± 1.9 vs. 14.4 ± 2.3 [p = 0.032] and 0.3 ± 0.1 vs. 0.2 ± 0.0 [p < 0.001], respectively). Using receiver operating characteristics curve analysis to predict abortion in AI patients, the highest area under the curve was found for SII (0.727 for SII and 0.666 for NLR). CONCLUSION: SII, NLR, MLR, RDW, and platelet to lymphocyte ratio (PLR) levels were significantly increased in patients with TA. This study supports the idea that several inflammatory pathways may play an important role in the pathogenesis of this disorder. SII may be a much better marker than NLR and PLR for predicting the inflammatory status of the disease and abortion in an ongoing pregnancy.

Predictive value of hyperglycosylated human chorionic gonadotropin for pregnancy outcomes in threatened abortion in first-trimester viable pregnancies / Valor predictivo de la hCG hiperglosilada para predecir resultado de la gestación en amenaza de aborto de primer trimestre en gestación viable

BACKGROUND: To investigate the value of a single determination of hyperglycosylated hCG (hCG-H) for predicting the clinical outcome of patients with threatened abortion in the first trimester of pregnancy. METHODS: Prospective study performed on 86 consecutively selected women with a diagnosis of threatened abortion and viable intrauterine pregnancy in the first trimester of pregnancy, conducted in two tertiary care hospitals. All patients underwent a single blood sample to determine hCG-H and total hCG serum levels and a transvaginal ultra-sound 12-24 hours after diagnosis. Patients were monitored to determine whether the outcome was a miscarriage before the 20th week of pregnancy. RESULTS: Forty-three women (50%) had a miscarriage during the follow-up. We observed a very high correlation between hCG-H and total hCG (r = 0.91, p < 0.001). Median hCG-H and total hCG from pregnancies with normal outcome was significantly higher than those ending in abortion. hCG-H and total hCG were very similar predictors of pregnancy outcomes (AUC: 0.90 and 0.89, respectively). The ratio hCG-H / total hCG was a poor predictor (AUC: 0.64). CONCLUSION: A single hCG-H assay is helpful for predicting pregnancy outcomes in women with first trimester threatened abortion and viable or potentially viable pregnancy at the time of presentation. However, hCG-H is not a better predictor than total hCG

FUNDAMENTO: Investigar el valor de una única determinación de hCG hiperglicosilada (hCG-H) para predecir el resultado clínico de pacientes con amenaza de aborto en el primer trimestre del embarazo. MÉTODOS: Estudio prospectivo realizado en 86 mujeres, seleccionadas consecutivamente, con diagnóstico de amenaza de aborto y embarazo intrauterino viable en el primer trimestre de embarazo, realizado en dos hospitales de tercer nivel. A todas las pacientes se les realizó una única extracción sanguínea para determinar los niveles séricos de hCG-H y hCG total, y una ecografía transvaginal 12-24 horas después del episodio de sangrado. Se realizó seguimiento de las pacientes para determinar si el resultado fue un aborto espontáneo antes de la semana 20 de embarazo. RESULTADOS: Cuarenta y tres mujeres (50%) sufrieron un aborto espontáneo durante el seguimiento. Se observó una correlación muy alta entre hCG-H y hCG total (r = 0,91, p < 0,001). La mediana de hCG-H y hCG total de los embarazos con resultado normal fue significativamente mayor que la de aquellos que terminaron en aborto. La hCG-H y la hCG total fueron predictores muy similares del resultado del embarazo (AUC: 0,90 y 0,89, respectivamente). La relación hCG-H / hCG total fue un mal predictor (AUC: 0,64). CONCLUSIÓN: La determinación única de hCG-H es útil para predecir el resultado del embarazo en mujeres con amenaza de aborto en el primer trimestre y embarazo viable en el momento de la presentación clínica. Sin embargo, la hCG-H no es mejor predictor que la hCG total

Novel approach using serum progesterone as a triage to guide management of patients with threatened miscarriage: a prospective cohort study.

Threatened miscarriage is a common gynaecological emergency, with up to 25% of women eventually progressing to spontaneous miscarriage. The uncertainty of pregnancy outcomes results in significant anxiety. However, there is currently no acceptable framework for triaging patients presenting with threatened miscarriage. We aim to evaluate the efficacy and safety of a novel clinical protocol using a single serum progesterone level to prognosticate and guide management of patients with threatened miscarriage. 1087 women presenting with threatened miscarriage were enrolled in the study. The primary outcome was spontaneous miscarriage by 16 weeks' gestation. Among the 77.9% (847/1087) of study participants with serum progesterone ≥ 35 nmol/L who were not treated with oral dydrogesterone, the miscarriage rate was 9.6% (81/847). This did not differ significantly from the 8.5% (31/364) miscarriage rate observed in our prior studies; p = 0.566. Among women with serum progesterone < 35 nmol/L who were treated with dydrogesterone, the miscarriage rate was 70.8% (170/240). Our novel clinical triage protocol using a single serum progesterone level allowed both effective risk stratification and a reduction in progestogen use with no significant adverse pregnancy outcomes. This protocol, based on a single serum progesterone cutoff, can be readily adapted for use in other healthcare institutions.

Can neutrophil-lymphocyte and platelet-lymphocyte ratios predict threatened abortion and early pregnancy loss?

OBJECTIVES: An investigation of the importance of hematological inflammatory markers on the prognosis of first trimester pregnancies and their role in predicting threatened abortion and early pregnancy loss. MATERIAL AND METHODS: This study was carried out in the Obstetrics and Gynecology Department of the Faculty of Medicine in our University between January 2018 and May 2019. Three-hundred individuals, 100 of them diagnosed with early pregnancy loss (EPL), 100 diagnosed with threatened abortion (TA) and 100 healthy control patients (HC), participated in the study. RESULTS: There were no statistically significant differences in terms of hemoglobin, platelet, neutrophil count and NLR between the three groups. The RBC counts were significantly lower in EPL and TA compared to HC. Similarly, it was determined that the MPV value was significantly lower in EPL compared to HC. On the other hand, there was no difference in MPV between TA and HC. The PLR was higher in EPL and TA. CONCLUSIONS: MPV, RBCs and PLR values were strongly associated with first-trimester miscarriage. These economical and easily measurable platelet indices can be used to predict fetal losses.

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.

Higher ꞵ-human chorionic gonadotropin and estrogen levels during the first 6 weeks of pregnancy are associated with threatened abortion.

The associations of human chorionic gonadotropin (hCG), estrogen, and progesterone levels with threatened abortion have not been fully studied. Eighty women with threatened abortion were recruited sequentially, and the levels in their pregnancy hormones during the first trimester were compared with that of 160 normal early pregnancy controls. The natural logarithm transformed (Ln) hCG and Lnestrogen of women with threatened abortion and gestational age ≤ 6 weeks were significantly higher than values for the normal controls of the same gestational age (8.6 ± 1.2 vs. 7.4 ± 1.7 mIU/mL and 5.8 ± 0.4 vs. 5.4 ± 0.5 pg/mL); the two hormones reached similar levels in the groups of gestational age > 6 weeks. Among the group with gestational age ≤ 6 weeks, a univariate logistic regression showed that LnhCG and Lnestrogen were associated with threatened abortion, with odds ratios (ORs) of 1.85 [95% confidence interval (CI): 1.30-2.64] and 4.62 (95% CI: 1.67-12.80), respectively. The multivariate logistic regression model revealed that hCG and estrogen were mutually confounding factors, and only hCG was an independent factor for threatened abortion (OR 1.56; 95% CI: 1.06-2.28). None of the variables in the univariate or multivariate logistic regression was a factor associated with threatened abortion after 6 weeks gestational age. In conclusion, ß-hCG and estrogen levels in the first half of the first trimester are factors associated with threatened abortion.

Change of the levels of trace elements and heavy metals in threatened abortion.

BACKROUND: This study aimed to investigate the impact of changes in the serum levels of trace elements and heavy metals in threatened abortion, which is a common complication in early pregnancy. Earlier studies have shown that changes in the serum levels of some trace elements and increased serum concentrations of heavy metals are associated with spontaneous abortion; however, this relationship has not been fully clarified. METHODS: The patient group consisted of 45 pregnant women diagnosed with threatened abortion. There were 40 healthy nonpregnant women in the control group. Blood samples were obtained from the patients and the healthy controls, and the concentrations of serum trace elements and heavy metals were measured using atomic absorption spectrophotometry. RESULTS: Statistically significant decreases were found in the serum zinc (Zn), iron (Fe), magnesium (Mg) and manganese (Mn) levels, and significant increases were found in the serum copper (Cu), cadmium (Cd) and lead (Pb) levels in cases of threatened abortion in comparison to the controls (p < 0.001). However, there was no difference between the groups in terms of the serum cobalt (Co) levels (p > 0.001). CONCLUSION: Changes in the balance of some essential trace elements (especially decreases in Fe and Zn) and elevated concentrations of some toxic heavy metals in the blood may be important diagnostic and prognostic parameters for threatened abortion.

Serum progesterone distribution in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation: a prospective cohort study.

BACKGROUND: Progesterone is a critical hormone in early pregnancy. A low level of serum progesterone is associated with threatened miscarriage. We aim to establish the distribution of maternal serum progesterone in normal pregnancies compared to pregnancies complicated by threatened miscarriage from 5 to 13 weeks gestation. METHODS: This is a single centre, prospective cohort study of 929 patients. Women from the Normal Pregnancy [NP] cohort were recruited from antenatal clinics, and those in the Threatened Miscarriage [TM] cohort were recruited from emergency walk-in clinics. Women with multiple gestations, missed, incomplete or inevitable miscarriage were excluded from the study. Quantile regression was used to characterize serum progesterone levels in the NP and TM cohorts by estimating the 10th, 50th and 90th percentiles from 5 to 13 weeks gestation. Pregnancy outcome was determined at 16 weeks of gestation. Subgroup analysis within the TM group compared progesterone levels of women who subsequently miscarried with those who had ongoing pregnancies at 16 weeks of gestation. RESULTS: Median serum progesterone concentration demonstrated a linearly increasing trend from 57.5 nmol/L to 80.8 nmol/L from 5 to 13 weeks gestation in the NP cohort. In the TM cohort, median serum progesterone concentration increased from 41.7 nmol/L to 78.1 nmol/L. However, median progesterone levels were uniformly lower in the TM cohort by approximately 10 nmol/L at every gestation week. In the subgroup analysis, median serum progesterone concentration in women with ongoing pregnancy at 16 weeks gestation demonstrated a linearly increasing trend from 5 to 13 weeks gestation. There was a marginal and non-significant increase in serum progesterone from 19.0 to 30.3 nmol/L from 5 to 13 weeks gestation in women who eventually had a spontaneous miscarriage. CONCLUSIONS: Serum progesterone concentration increased linearly with gestational age from 5 to 13 weeks in women with normal pregnancies. Women with spontaneous miscarriage showed a marginal and non-significant increase in serum progesterone. This study highlights the pivotal role of progesterone in supporting an early pregnancy, with lower serum progesterone associated with threatened miscarriage and a subsequent complete miscarriage at 16 weeks gestation.

The randomised controlled trial of micronised progesterone and dydrogesterone (TRoMaD) for threatened miscarriage.

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

Serum levels of human epididymis protein 4 are more stable than cancer antigen 125 in early and mid-term pregnancy.

AIM: Previous studies have shown serum human epididymis protein 4 (HE4) and cancer antigen 125 (CA125) levels could serve as predictive markers in the diagnosis of ovarian cancer. However, HE4 levels have been less well studied during pregnancy, especially in threatened abortion, while CA125 levels were fluctuated. Our study aimed to assess the stability of HE4 and CA125 levels through trimesters and in cases of threatened abortion. METHODS: Forty-six nonpregnant women (control), 167 healthy pregnant women and 46 pregnant threatened abortion (TA; 8-12 weeks pregnancy) women who visited the Obstetrics and Gynecology Hospital of Fudan University from September to December 2017 were recruited. The healthy pregnant women group included 57 women in the first trimester (T1), 55 in the second (T2) and 55 in the third (T3). Serum levels of HE4 and CA125 were measured by electrochemiluminescent immunoassay. RESULTS: Both HE4 and CA125 levels in the T3 group were significantly higher than in the control group (P < 0.001). There was no difference in HE4 between the control, T1 and T2 groups, while levels of CA125 in T1 group were elevated (P < 0.001). There was no difference in HE4 levels between the TA, control and T1 groups. However, the levels of CA125 in the TA group were much higher (P < 0.05). CONCLUSION: The level of HE4 was found to be more stable than that of CA125 in early and mid-pregnancy and in cases of threatened abortion.

Doppler and biochemical assessment for the prediction of early pregnancy outcome in patients experiencing threatened spontaneous abortion.

OBJECTIVE: To evaluate the usefulness of Doppler indices of the corpus luteum and uterine artery in combination with serum progesterone and cancer antigen 125 (CA125) as prognostic tools in first-trimester threatened spontaneous abortion. METHODS: Pregnant women with threatened spontaneous abortion at a pregnancy duration 8-10 weeks were enrolled into an observational prospective clinical trial at a university hospital in Egypt during 2015. Doppler indices (uterine artery/corpus luteum resistance index and pulsatility index) and biochemical markers (CA125, progesterone) were determined and compared by pregnancy outcome (spontaneous abortion vs continuing pregnancy at 20 weeks). RESULTS: Of 100 women included, 16 had a spontaneous abortion. These women had a higher CA125 value than did women without an abortion (P<0.001), whereas the progesterone level among women with an abortion was lower (P<0.001). The Doppler indices were not significantly different between the groups, but calculation of the uterine artery resistance index as a percentage of the normal standard value at a given pregnancy duration revealed significant differences (P<0.001) between the two groups. CONCLUSION: Serum progesterone and CA125 are useful provisional predictors of spontaneous abortion, whereas the Doppler indices are not. The two biomarkers could be used as a basis to counsel anxious couples. CLINICALTRIALS.GOV: NCT02420769.

Same-day confirmation of intrauterine pregnancy failure in women with first- and early second-trimester bleeding.

OBJECTIVE: To determine if alpha-fetoprotein (AFP) concentration in vaginal blood, in the setting of dissolved fetal tissue, is significantly higher than its concentration in the maternal serum. DESIGN: A prospective cohort study. SETTING: Medical center. PATIENT(S): Four groups of women were evaluated: 1) with missed/incomplete miscarriage with vaginal bleeding; 2) with threatened miscarriage; 3) with vaginal bleeding during cerclage placement; and 4) undergoing dilation and curettage (D&C). INTERVENTIONS(S): None. MAIN OUTCOME MEASURE(S): In each patient, AFP concentration in the vaginal blood or in the liquid component of the evacuated products of conception (POC; D&C group) was compared with the AFP concentration in the maternal serum. RESULT(S): The median (range) concentration ratios of AFP in vaginal blood (or POC) to AFP in maternal serum were 24.5 (5.1-8,620) and 957 (4.6-24,216) for the missed/incomplete (n = 30) and the D&C (n = 22) groups, respectively, whereas they were only 1.2 (0.4-13.4) and 1.01 (0.7-1.5) for the threatened miscarriage (n = 15) and cerclage (n = 9) groups, respectively. Receiver operating characteristic (ROC) analysis demonstrated 100% sensitivity and 86.7% specificity for the detection of the passage of fetal tissue (ratio 4.3, area under the ROC curve 0.96). CONCLUSION(S): Higher concentrations of AFP in vaginal blood than in maternal serum may indicate the presence of dissolved fetal tissue (i.e., confirming a failed pregnancy).

Serum Galectin 7 is Not Useful to Predict Abortion in the First Trimester.

OBJECTIVE: Galectins are animal lectins that bind to surface glycoproteins expressed at the fetal-maternal interface. The aim of this prospective case-control study was to investigate the possible relationship between levels of maternal serum galectin-7 and threatened abortion (TA) and to determine whether serum galectin-7 had any prognostic value. METHODS: This prospective study was conducted between August 2014 and February 2015. Included in the study were 31 consecutive pregnant women who were hospitalized for TA between 6 and 14 weeks of gestation and 33 healthy gestational age matched pregnant women without any symptoms of miscarriage. Serum galectin-7 levels were measured via ELISA. RESULTS: The mean serum galectin-7 levels of the two groups were not significantly different (31 TA patients: 2.84 ± 0.43 pg/mL, 33 controls: 2.785 ± 0.32 pg/mL, p = 0.543). Six pregnancies in the TA group resulted in abortion (19.4%). CONCLUSION: Serum galectin-7 was not useful for predicting prognosis in TA.

Validation of serum progesterone <35nmol/L as a predictor of miscarriage among women with threatened miscarriage.

BACKGROUND: Our recent paper, based on a pilot cohort of 119 women, showed that serum progesterone <35 nmol/L was prognostic of spontaneous miscarriage by 16 weeks in women with threatened miscarriage in early pregnancy. Using a larger cohort of women from the same setting (validation cohort), we aim to assess the validity of serum progesterone <35 nmol/L with the outcome of spontaneous miscarriage by 16 weeks. METHODS: In a prospective cohort study, 360 pregnant women presenting with threatened miscarriage between gestation weeks 6-10 at a tertiary hospital emergency unit for women in Singapore were recruited for this study. The main outcome measure measured is spontaneous miscarriage prior to week 16 of gestation. Area under the ROC curve (AUC) and test characteristics (sensitivity, specificity, positive and negative predictive value) at a serum progesterone cutpoint of <35 nmol/L for predicting high and low risk of spontaneous miscarriage by 16 weeks were compared between the Pilot and Validation cohorts. RESULTS: Test characteristics and AUC values using serum progesterone <35 nmol/L in the validation cohort were not significantly different from those in the Pilot cohort, demonstrating excellent accuracy and reproducibility of the proposed serum progesterone cut-off level. CONCLUSIONS: The cut-off value for serum progesterone (35 nmol/L) demonstrated clinical relevance and allow clinicians to stratify patients into high and low risk groups for spontaneous miscarriage.

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.

[Effects of Gushen Antai pills combined with progestin on serum ß-HCG, P, E2 and CA125 in patients with threatened abortion].

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

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.

How can we better predict the risk of spontaneous miscarriage among women experiencing threatened miscarriage?

This study seeks to establish progesterone and progesterone-induced blocking factor (PIBF) levels as predictors of subsequent completed miscarriage among women presenting with threatened miscarriage between 6 and 10 weeks of gestation. Our secondary objective was to assess the known maternal risk factors, toward development of a parsimonious and clinician-friendly risk assessment model for predicting completed miscarriage. In this article, we present a prospective cohort study of 119 patients presenting with threatened miscarriage from gestation weeks 6 to 10 at a tertiary women's hospital emergency unit in Singapore. Thirty (25.2%) women had a spontaneous miscarriage. Low progesterone and PIBF levels are similarly predictive of subsequent completed miscarriage. Study results (OR, 95% CI) showed that higher levels of progesterone (0.91, 95% CI 0.88-0.94) and PIBF (0.99, 95% CI 0.98-0.99) were associated with lower risk of miscarriage. Low progesterone level was a very strong predictor of miscarriage risk in our study despite previous concerns about its pulsatile secretion. Low serum progesterone and PIBF levels predicted spontaneous miscarriage among women presenting with threatened miscarriage between gestation weeks 6 to 10. Predictive models to calculate probability of spontaneous miscarriage based on serum progesterone, together with maternal BMI and fetal heart are proposed.