Effect of subchorionic hematoma on first-trimester maternal serum free ß-hCG and PAPP-A levels.

Objective: This study aimed to investigate the effects of the presence of subchorionic hematoma (SH) in early pregnancies with threatened miscarriage (TM) on levels of first-trimester maternal serum markers, pregnancy-associated plasma protein-A (PAPP-A), and free ß-human chorionic gonadotropin (ß-hCG) levels. Methods: The data of TM cases with SH in the first trimester between 2015 and 2021 were evaluated retrospectively. The data of age and gestational age-matched TM cases without SH were also assessed to constitute a control group. Demographic characteristics, obstetric histories, ultrasonographic findings, and free ß-hCG and PAPP-A levels of the groups were compared. Results: There were 119 cases in the study group and 153 cases in the control group. The median vertical and longitudinal lengths of the SH were 31 mm and 16 mm. The median age of both groups was similar (p=0.422). The MoM value of PAPP-A was 0.088 (.93) in the study group and 0.9 (0.63) in the control group (p=0.519). Similarly, the MoM value of free ß-hCG was 1.04 (0.78) in the study group and 0.99 (0.86) in the control group (p=0.66). No significant relationship was found in the multivariate analysis between free ß-hCG MoM, PAPP-A MoM, age, gravida, and vertical and longitudinal lengths of the hematoma (p>0.05). Conclusion: The level of PAPP-A and free ß-hCG were not affected by the SH. Therefore, these markers can be used reliably in TM cases with SH for the first-trimester fetal aneuploidy screening test.

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).

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.

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.

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.

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.

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.

The relationship between the VEGF/sVEGFR-1 ratio and threatened abortion.

PURPOSE: The aim of this study was to evaluate the levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor-1 (sVEGFR-1) and placenta growth factor (PlGF) and VEGF/SVEGFR-1 ratio in pregnant women with threatened abortion (TA) compared to uncomplicated pregnancies at the same gestational week. METHODS: Thirty-three pregnant women with TA and thirty-three pregnant women with uncomplicated pregnancies were included in this case-control study. The level of VEGF, sVEGFR-1, and PIGF was analyzed by enzyme-linked immunosorbent assay (ELISA). The primary purpose of this study was to compare the VEGF, sVEGFR- 1, and PlGF levels and VEGF/sVEGFR-1 ratios in pregnant women with TA and pregnant women with uncomplicated pregnancies. The secondary purpose of this study was to evaluate the correlation between serum levels of these markers and gestational age. RESULTS: The serum levels of the sVEGFR-1 [0.60 (0.21-1.68) vs. 0.24 (0.09-0.57) ng/ml], VEGF [39.10 (6.57-163.56) vs. 5.24 (0.84-15.08) ng/ml] and VEGF/SVEGFR-1 ratio [68.64 (6.45-550.48) vs 24.12 (2.63-72.63)] were significantly elevated in women with TA (respectively, p: 0.001, p: 0.001, p: 0.001). However, PlGF did not elevate in women with TA [20.80 (3.13-93.11) vs 20.16 (1.22-49.91) ng/ml] (p: 0.473). CONCLUSION: These findings support the hypothesis that increased levels of the VEGF and sVEGFR-1 and VEGF/SVEGFR-1 ratio may be associated with the pathogenesis of TA.

The value of placental protein 13, ß-human chorionic gonadotropin and progesterone in the prediction of miscarriages in threatened miscarriage patients.

The aim of this paper was to investigate the levels of maternal serum placental protein13 (PP13), beta human chorionic gonadotropin (ß-hCG) and progesterone in the prediction of miscarriages in threatened miscarriages. A total of 110 patients with a gestational age < 14 weeks were included in the study. A total of 42 patients were allocated as the study group (threatened miscarriage) and 68 patients were allocated as controls. A total of six miscarriages were observed in the study group. ß-hCG levels were significantly lower in the group with threatened miscarriage when compared with controls (p = 0.018). There was no statistically significant difference in regard to progesterone and PP13 levels occurred between two groups (p = 0.653 and p = 0.062, respectively). Following receiver operating characteristic (ROC) analysis, the ß-hCG parameter was found useful in differentiating miscarriages from the threatened miscarriage group (p = 0.031). PP13 and progesterone parameters in predicting miscarriages were not found as statistically significant (p = 0.084 and p = 0.914, respectively). This study suggests that ß-hCG measurements could be useful in predicting spontaneous miscarriage in women presenting with threatened miscarriage. Even though PP13 seems unfeasible to be used as a predictive marker for miscarriage, factors affecting PP13 levels should be considered along with the need for comprehensive studies including larger patient populations.

Association of kisspeptin-10 levels with abortus imminens: a preliminary study.

PURPOSE: To investigate the association between kisspeptin 10 (Kp-10) levels and early pregnancy bleeding and perinatal outcome. METHODS: A total of 20 pregnant women with the complaint of vaginal bleeding during 7-18 gestational weeks and 20 healthy gestational week matched pregnant women were included in the study. Maternal plasma Kp-10 levels were measured with the enzyme immunoassay method. Adverse pregnancy outcomes like intrauterine growth restriction, preterm delivery, preeclampsia and low birth weight were evaluated in both groups. RESULTS: Maternal plasma Kp-10 levels (p = 0.01) and birth weight (p = 0.06) were found to be lower in women with bleeding. Intrauterine growth restriction, preterm delivery and intrauterine exitus were noted more commonly in women with bleeding (10 vs. 0%, 25 vs. 15% and 20 vs. 0%, p = 0.08). Preeclampsia were developed in 5% of both groups. Kp-10 levels showed positive correlation with gestational week (p = 0.02) and ALT levels (p = 0.02). CONCLUSION: [corrected] Kp-10 levels were found lower in women with early pregnancy bleeding.

Obstetric outcome and cytokine levels in threatened miscarriage.

OBJECTIVES: To evaluate the proportion of women with threatened miscarriage (TM) who proceed to miscarriage in a population of single ethnicity and to investigate prospectively their risk of adverse pregnancy outcome in relationship with the cytokines levels in their circulation. METHODS: We conducted a prospective observational study over a period of 1 year of 94 Maltese women presenting with TM at the same hospital and compared their clinical data with those of 564 age-matched controls from the National Obstetric Information System (NOIS) of Malta. Main outcome measures included gestational age and weight at delivery and incidence of adverse pregnancy outcomes. A pilot study was carried out, where in subgroups of 10 women with TM (n=10), non-pregnant women (n=12), normal pregnant controls (n=9) and women presenting with missed-miscarriage (n=11), the plasma levels of ß-human chorionic gonadotrophin (ß-hCG), tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin-6 (IL-6), interleukin-10 (IL-10) and TNF-receptors 1 (R1) and 2 (R2) were measured. RESULTS: Of the women presenting with TM, 25 (26.6%) proceeded to complete miscarriage. The TM group had also a significantly higher incidence of antepartum haemorrhage (p<0.005), pre-eclampsia (p<0.05), foetal growth restriction (p<0.05), premature labour (p<0.001) and retained placenta (p<0.005). In the pilot biochemical analysis, significantly (p<0.05) higher levels of TNFα and lower levels of TNFR2 were found in the TM subgroup compared to non-pregnant controls. The ratio TNFα/IL-10 was significantly (p<0.05) higher and the ß-hCG levels was significantly lower (p<0.01) in missed-miscarriage and non-pregnant subgroups than in TM and normal pregnant controls. The IFNγ/1L-10 and IFNγ/1L-6 ratio were significantly (<0.001) different between the four subgroups with the lowest level found in TM. No similar gradient was found for the TNFα/1L-6 ratio. CONCLUSION: Women presenting with TM are at significantly increased risk of adverse pregnancy outcome and the pathophysiology of these conditions involves a change in the Th1/Th2 balance. Changes in levels of cytokines could help to predict and thus prevent the development of some of these complications.