Prognostic value of immunoglobulin determination in women with threatened abortion

Determinations of immunoglobulins IgG, IgA and IgM were performed with serum and uterine blood of women who suffered from threatened abortion. In 40 of the examined women the pregnancy could be maintained and finished with normal delivery, and in 40 other women spontaneous abortion happened. Mean values of IgG, IgA and IgM of serum and uterine blood were significantly higher in women with spontaneous abortion than in women with delivery. Prognosis of threatened abortion is more unfavourable, if concentrations of immunoglobulins in serum and especially in uterine blood increase.     

The detection of anti-beta2-glycoprotein I antibodies is associated with increased risk of pregnancy loss in women with threatened abortion in the first trimester

OBJECTIVE: This study was designed to evaluate whether the detection of serum antiphospholipid autoantibodies may be useful in predicting pregnancy outcome in women with threatened abortion in the first trimester. STUDY DESIGN: A group of 77 pregnant women of between 8 and 12 weeks' gestation with vaginal bleeding was tested for serum antiphospholipid, lupus anticoagulants, anticardiolipin, antinuclear antibodies, and anti-beta2-glycoprotein I antibodies, and was followed up until the spontaneous end of pregnancy. A control group composed of 15 healthy women with uncomplicated gestation was tested contemporarily for the same antibody panel. RESULTS: Of the 77 patients with threatened abortion, 32 (41.5%) progressed to deliver at term and 45 (58.5%) experienced early pregnancy loss. Among the antibodies evaluated, only anti-beta2-glycoprotein I was significantly more frequent in those women whose pregnancy resulted in spontaneous abortion (22/45, 49%) than in those who progressed to term (6/32, 19%) or in the control group (2/15, 13%; p=0.004). This difference was specific to the IgM isotype (p=0.001). After adjustment by multivariate analysis, the odds ratio for pregnancy loss associated with a positive beta2-glycoprotein I antibody test was 5.18 (p=0.001). CONCLUSION: The detection of anti-beta2-glycoprotein I antibodies is associated with an increased risk of pregnancy loss in women with threatened abortion in the first trimester.     

Lymphocytic progesterone receptors in normal and pathological human pregnancy

The progesterone receptor-specific monoclonal antibody (MoAb) mPRI was tested for its reactivity towards peripheral blood lymphocytes (PBL) of 49 healthy pregnant women, nine pregnant women with clinical symptoms of threatened preterm delivery, seven women with recurrent spontaneous abortion, ten women in labour and ten women with spontaneous abortion. Lymphocytes of 12 healthy age-matched non-pregnant volunteers were used as controls. Lymphocytes of nine healthy pregnant women at the 1st trimester of pregnancy and those of two non-pregnant donors were tested for the presence of estrogen and progesterone receptors by enzyme immunoassay. PBL of healthy pregnant women contained significantly more positive cells than those of non-pregnant controls. Furthermore, the number of receptor-containing cells increased in parallel with gestational age. In blood samples drawn during labour, as well as in those obtained from women with spontaneous abortion or clinical symptoms of threatened pre-term delivery, the percentage of positively stained lymphocytes was significantly lower than normal pregnancy values. This was also the case in peripheral blood of pregnant women with a history of recurrent spontaneous abortions.     

The value of ovarian and placental steroid determinations in abnormal early pregnancy

Concentrations of estradiol (E2), progesterone (P), and 170H-progesterone (170H-P) were measured by radioimmunoassay in serum samples obtained from a group of 98 women with threatened (n = 60), incomplete (n = 22) or missed (n = 16) abortion between the 4th and 17th week of pregnancy. The diagnosis was based on the clinical symptoms and the results of ultrasound scanning. In threatened abortion 54, out of 60 E2 values were within the 95% normal range, including most of the cases in which abortion occurred later. In incomplete abortion 18 of 21 E2 values were below the lower 95% confidence limit. In missed abortion, 11 of 15 E2 values were abnormal, being below the 95% normal range. Similar patterns in women with threatened, incomplete or missed abortion can be observed for values of P and 170H-P. Our results indicate that serum determinations of ovarian and placental steroids in women with early pregnancy failure are not of great clinical value.     

Can a single serum CA125 assay predict the outcome of threatened abortion?

Earlier work suggested that high levels of CA125 could be detected in the sera of women with threatened abortion. In this study, we used CA125 as a method of anticipating outcome in cases of threatened abortion and compared the results with ultrasonic findings. Three groups of patients were studied.(1) 57 women who threatened to abort, but whose pregnancy continued.(2) 43 women with a threatened abortion, who subsequently aborted, and (3) 50 normal women who had no bleeding in early pregnancy. There was a highly significant increase in serum CA125 in women who aborted compared with the other two groups (P<0.001). The results compared well with conventional ultrasound and serum CA125 may be developed as a cheap, sensitive and specific predictor of outcome in cases of threatened abortion.     

Can pregnancy-associated plasma protein A (PAPP-A) predict the outcome of pregnancy in women with threatened abortion and confirmed fetal viability?

Depressed pregnancy-associated plasma protein A (PAPP-A) concentrations have been found in patients with threatened abortion, often weeks before spontaneous abortion while the fetus was still alive. In order to extend these findings we have developed a highly sensitive PAPP-A radio-immunoassay and have established a reference range in early pregnancy for PAPP-A between week 7 and week 20 of pregnancy, based on blood samples from 240 pregnant women. The gestational age was determined by ultrasound. PAPP-A was measured in 128 women admitted to hospital because of vaginal bleeding in the 7th to 20th gestational week. The viability of the fetus was confirmed by ultrasonography. The serum values of PAPP-A were significantly lower (p = 0.002) in the group of women with vaginal bleeding than in the group of normally pregnant women. However, with regard to abortion later on, the predictive value of an abnormal blood test on admission was only 18.7%. Serial determinations showed increased PAPP-A values corresponding to the centile expected in the 12 women who aborted, as well as in the 116 women who gave birth. Consequently, the test is of no clinical value in the assessment of the prognosis in patients with symptoms of threatened abortion.     

T-helper 2-cytokine levels in women with threatened abortion

OBJECTIVE: Considering that successful embryo development has been immunologically attributed to a T-helper 2 phenomenon and that threatened abortion is a very frequent but pathogenetically not well-defined clinical entity, our purpose was to investigate serum levels of the main T-helper 2-type cytokines during the evolution of this condition. STUDY DESIGN: Three T-helper 2-type cytokines (interleukin-6 (IL-6), interleukin-10 (IL-10), interleukin-13 (IL-13)) were measured by an enzyme-linked immunosorbent assay (ELISA) in serum of 12 women with threatened abortion both at hospital admission and discharge time. Fourteen women with missed abortion, 14 normal pregnant women and 14 normal non-pregnant women represent study control groups. RESULTS: Serum concentrations of the selected T-helper 2-type cytokines showed no significant differences in women with threatened abortion with those of normal pregnant and non-pregnant women, whereas showed significantly lower values in women with missed abortion. CONCLUSION: Our data (a) confirm the concept that first-trimester normal pregnancy is a T-helper 2 phenomenon, (b) show that threatened abortion, when T-helper 2-biased, may tend to a positive evolution of the condition, (c) display that interleukin-10, particularly, may represent a useful diagnostic and prognostic marker for predicting the normal continuance of the pregnancy in threatened abortion, (d) confirm the existence of a T-helper 2-type pattern deficiency in missed abortion, and finally (e) may open the way to new T-helper 2-biased immune therapies in case of difficult first-trimester pregnancies.     

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.     

Midwifery triage of first trimester bleeding

Approximately one of five pregnant women will experience bleeding during the first trimester of pregnancy. Of these women, about half will go on to have a spontaneous abortion. Comfort with triaging this common problem assists the midwife in providing quality, cost-effective care without eliminating continuity. This article reviews the causes of early pregnancy bleeding, offers strategies to differentiate between these causes, and identifies emergent from nonemergent presentations. Triage and management strategies for women with an impending or threatened spontaneous abortion are reviewed, exploring the alternative of expectant management.     

Prognostic value of the pregnancy zone protein during early pregnancy in spontaneous abortion

The concentration of pregnancy zone (PZ) protein in maternal serum during early normal pregnancy was followed in a prospective study of 261 pregnant women. A marked increase which followed an exponential function was found and a theoretic onset of induction at the time for implantation was calculated. Women with a later spontaneous abortion had low values. The prognostic relevance of PZ determinations was studied and values from women who later had a spontaneous abortion were compared to those from normal pregnancies. The prognostic value of PZ protein was compared to that of hCG and progesterone. PZ and hCG assays had the same prognostic accuracy concerning the outcome of pregnancy while determinations of progesterone were less valuable.     

Serum estradiol as an aid in the diagnosis of ectopic pregnancy.

The value of serum beta-hCG measurement in the diagnosis of ectopic pregnancy is well established, and there have been recent studies on the use of serum progesterone levels. However, we have been unable to find any reports on the potential application of serum estradiol (E2) assays in the diagnosis of ectopic pregnancy. We therefore concurrently measured serum E2, progesterone, and beta-hCG in 100 women with ectopic pregnancies, as well as in 69 controls with normal intrauterine pregnancies and 36 women with threatened abortion. The mean (+/- standard deviation) E2 levels for ectopic-pregnancy patients, the normal controls, and the women with threatened abortion were 281.1 +/- 115.6, 788.2 +/- 45.5, and 788.8 +/- 40.6 pg/mL, respectively; the mean levels in the ectopic group were significantly different (P less than .0001) from those of the other two groups. All but one of the ectopic pregnancies had values below 650 pg/mL for E2 and 23 ng/mL for progesterone, and all but one of the normal intrauterine pregnancies had values above these levels. Our data suggest that the addition of the estradiol assay, with or without progesterone, to the early evaluation of patients suspected of having an ectopic pregnancy may be helpful in diagnosis.     

表皮生长因子及其受体与流产关系的探讨

采用放射免疫竞争抑制饱和分析法，检测４７例难免流产患者，６５例人工流产及２０例健康非孕妇女血清表皮生长因子（ＥＧＦ）水平；同时采用免疫组织化学法检测流产者胚胎组织中表皮生长因子受体（ＥＧＦＲ）表达程度。结果：人工流产组血清ＥＧＦ水平高于自然流产及非孕妇女，而自然流产与非孕妇女差异无显著性；胚胎组织中ＥＧＦＲ阳性表达率人工流产组明显高于自然流产组。提示：ＥＧＦ通过与其受体结合对妊娠维持、胚胎及胎儿的     

Transplacental hemorrhage during spontaneous and induced abortions

Blood smears were examined for the presence of fetal cells in 122 women who had spontaneous or induced abortions in an effort to determine the incidence and magnitude of fetomaternal hemorrhage after abortion. Smears from cord blood of newborn infants served as positive control smears. The amount of fetal blood that had crossed the placental barrier was determined before and after spontaneous and induced abortions in the 1st and 2nd trimester of pregnancy. The incidence of fetomaternal hemorrhage was 2.9% in the 1st trimester and as high as 11.1% in those cases who showed signs of choriodecidual disruption as in threatened abortions. The incidence was slightly higher in 2nd trimester as 6.2% in symptomless cases; it was significantly higher, 22.7%, in cases presenting with vaginal bleeding. The incidence was more in patients who had undergone surgical intervention. In the induced abortion too, the cells score percentage was higher following operation, although it was less as compared to spontaneous abortions.     

5-Hydroxytryptamine (serotonin), copper and ceruloplasmin plasma concentrations in spontaneous abortion.

Ceruloplasmin, the blue copper-protein of the blood plasma, is believed by some workers to be involved in the metabolic management of 5-hydroxytryptamine (serotonin) during pregnancy. 5-Hydroxytryptamine is abortifacient in experimental animals. By some authors, a role has been suggested for it in human abortion. The plasma concentrations of 5-hydroxytryptamine, copper and ceruloplasmin were measured in non-pregnant women, in normal early pregnancy and in cases of spontaneous abortion. Compared with normal early pregnancy, cases of inevitable abortion show lower values for both plasma copper and ceruloplasmin and higher values for plasma 5-hydroxytryptamine. The possible implications of these findings are discussed in view of the alterations in ceruloplasmin values in pregnancy and in the light of what is known of the pharmacology and metabolism of 5-hydroxytryptamine. It it believed that these alterations in plasma copper, ceruloplasmin and 5-hydroxytryptamine in cases of inevitable abortion are the effect, rather than the cause, of abortion.     

复发性流产患者孕早期血清性激素结合球蛋白和胰岛素抵抗指数特征研究

目的 探讨复发性流产患者孕早期血清性激素结合球蛋白（sex hormone binding globulin,SHBG）和胰岛素抵抗指数的特征。方法 选择2011年6月至2013年6月在中国医科大学附属盛京医院就诊的有复发性流产史孕妇122例为病例组,56例同期就诊无不良孕产史健康早孕妇女为对照组。于妊娠8～10周收集病例组及对照组个人资料和血清标本。检测指标为SHBG、空腹血糖（FPG）、空腹胰岛素（FINS）、雌二醇（E2）、睾酮（T）、硫酸脱氢表雄酮（DHEAS）。血清SHBG采用酶联免疫吸附试验(ELISA)法测定,FPG采用氧化酶法测定,FINS、E2、T、DHEAS采用化学发光免疫分析法测定。 结果 （1）病例组和对照组孕妇身高、舒张压和检测时孕周比较差异无统计学意义（P>0.05）;两组孕妇年龄、体重、体重指数、收缩压、孕次和既往流产史比较差异有统计学意义（P<0.05）。（2）与对照组比较,病例组孕妇SHBG水平显著降低,FPG、FINS、胰岛素抵抗指数（HOMA-IR）和DHEAS显著升高,差异均有统计学意义（P<0.01）;E2和T水平比较差异无统计学意义（P>0.05）。（3）多因素分析显示身高、体重指数、SHBG和DHEAS是复发性流产的影响因素（P<0.05）。结论 有复发性流产史患者孕早期SHBG较正常孕妇降低,胰岛素抵抗指数较正常孕妇升高,SHBG是复发流产的影响因素之一。     

Urinary pregnandiol-3-glucuronide and estrone conjugates to creatinine ratios in early pregnancies complicated by vaginal bleeding

There is no simple and rapid test available to predict the outcome of an early pregnancy complicated by vaginal bleeding. In this prospective study, 15 women with normal pregnancies collected a weekly urine sample between 6 and 13 weeks' gestation. A single random urine sample was obtained from 15 women with bleeding who continued to carry their child and 50 women who proceeded to have a spontaneous abortion (SAB). Pregnandiol-3-glucuronide (PDG) was determined with the use of enzyme-multiplied immunoassay technique (EMIT) and estrone conjugates (E1C) were measured by radioimmunoassay (RIA). The ratios of these metabolites to creatinine (C) were calculated. PDG/C ratios in normal women rose gradually from 6 weeks on. All women with bleeding during a normal pregnancy had ratios in the normal range, but 94% of women with a SAB had ratios below the normal range. The E1C/C ratio remained unchanged from 6 to 11 weeks and then rose rapidly. Until 11 weeks, there was no clear separation between the E1C/C ratios of the women with a SAB and the women with bleeding who continued their pregnancies. The prognosis of threatened abortion can be made by a urinary PDG/C ratio but not by an E1C/C ratio. EMIT is simple and quick and uses technology present in many laboratories.     

Spontaneous abortion--an infectious aetiology?

The role of Chlamydia trachomatis, genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C. trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C. trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

Spontaneous abortion-an infectious aetiology?

Summary. The role of Chlamydia trachomatis , genital mycoplasmas, Campylobacter spp. and other aerobic and anaerobic bacteria in the aetiology of spontaneous abortion was investigated prospectively in 241 pregnant women at a community hospital. Sixteen women who had threatened abortions were a little younger, of lower social class and had had more previous spontaneous abortions than the 76 women who aborted or the 149 women whose pregnancies were not complicated in the early stages by haemorrhage. The demographic characteristics of the latter two groups of women were similar. C.trachomatis was isolated from the cervix of only one woman and she had no genital-tract bleeding at any stage in her pregnancy. Mycoplasma hominis was isolated most often from the women who had threatened abortions but otherwise the prevalence of the other various micro-organisms was similar in women who had spontaneous abortions, threatened abortions, and in those who had pregnancies uncomplicated by vaginal bleeding. It was clear, therefore, that C.trachomatis played no role in the aetiology of spontaneous abortion in the population studied and there was no suggestion that any of the other micro-organisms were involved either.     

cFLIP在早期自然流产绒毛组织的表达及意义

目的:检测早期正常妊娠及自然流产绒毛组织中细胞凋亡抑制蛋白cFLIPmRNA及其蛋白产物的表达,分析并探讨cFLIP与自然流产的关系。方法:应用RT-PCR法及免疫组化SP法检测cFLIP mRNA及其蛋白产物在20例自然流产患者(研究组)绒毛组织的表达,以同期正常妊娠要求人工流产20例为对照组。结果:研究组绒毛组织中cFLIP mRNA及蛋白表达明显低于对照组,差异有统计学意义(P<0.01)。结论:细胞凋亡抑制蛋白cFLIP参与维持正常妊娠,绒毛组织中其表达下降可能在自然流产的发生中起重要作用。     

Prognostic value of repeated serum CA 125 measurements in first trimester pregnancy.

OBJECTIVE: To assess the diagnostic value of maternal CA 125 in patients with symptomatic first trimester pregnancy and to evaluate the prognostic significance of CA 125 versus beta-hCG in early pregnancies with intact fetal heartbeat, complicated by vaginal bleeding. STUDY DESIGN: Two prospective open-label studies with longitudinal follow-up in the second trial. SETTING: Academic Department of Obstetrics and Gynecology, University of Cologne. PATIENTS: Study 1: 168 patients presenting between gestational weeks 6 and 12 with: extrauterine pregnancy, 29; missed abortion, 50; incomplete spontaneous abortion, 38; imminent abortion, 33; and normal pregnancy (no history of endometriosis or ovarian mass), 18. Study 2: Fifty consecutive patients with vaginal bleeding during gestational weeks 6-12 all of whom having demostrable fetal heartbeat. Eighteen patients finally aborted whereas the remainder had normally continuing pregnancy until term. MAIN OUTCOME MEASURE: Study 1: Single serum determinations of CA 125 and beta-hCG were correlated with the different disorders observed. Study 2: Two sequential measurements of serum CA 125 and beta-hCG performed within a 5-7 days interval were related to the outcome of pregnancy as indicated by changes of the ultrasound presentation, miscarriage, future hospitalization, or delivery. RESULTS: Study 1: Patients with vaginal bleeding generally had higher median CA 125 values (38 IU/ml; range 1.3-540) compared to non-bleeding patients (17.8 IU/ml; range 1.0-157). No statistically significant differences in regard to median serum CA 125 levels between symptomatic and normal pregnancies occurred: normal pregnancy, 25.5 IU/ml (range 3.2-97); ectopic pregnancy, 26 IU/ml (range 1.3-157); missed abortion, 19.1IU/ml (range 1-242); threatened abortion, 48 IU/ml (range 5.2-540); spontaneous abortion, 40 IU/ml (range 5.4-442). Study 2: Initial CA 125 levels did not differ significantly between both groups of patients with 27/32 non-aborters and 13/18 aborters showing concentrations below 65 IU/ml. After 5-7 days, CA 125 in all patients who eventually aborted remained high or increased whereas non-aborters all had constantly low or steeply declining CA 125 measures. beta-hCG increased in all non-aborters but also in 13/18 aborters during the 5-7 day interval. CONCLUSION: Single serum measurements of CA 125 in symptomatic first trimester pregnant patients failed to discriminate spontaneous abortion, ectopic or normal pregnancies. However, sequential determinations of maternal CA 125 measurements appear to be a highly sensitive prognostic marker in patients with viable pregnancy at risk for abortion.