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.

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.

Alterted SLIT2/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy.

AIMS: Two-thirds of early pregnancy failures present with reduced trophoblast invasion, and SLIT2/ROBO1 signalling is considered to play an important role in trophoblast function during pregnancy. We investigated SLIT2/ROBO1 signalling associated with missed and threatened miscarriage during early gestation. METHODS AND RESULTS: Human placenta samples were collected from women with missed miscarriage (n = 25), threatened miscarriage (n = 22) and termination of pregnancy controls (n = 32). Corresponding decreases in beta human chorionic gonadotrophin (ß-hCG) levels and shallow trophoblast invasion were observed in patients with missed and threatened miscarriage, immunohistological staining revealed abnormal Slit2 and Robo1, as well as E-cadherin and activating protein-2 alpha (AP-2α) expression in villi and extravillous trophoblasts, and the expression of these proteins were confirmed in villi and decidua of miscarriage material by Western blotting. Using HTR8/SVneo cells, blocking SLIT2/ROBO1 signalling promoted cell migration, proliferation and suppressed differentiation. Moreover, blocking SLIT2/ROBO1 signalling in HTR8/SVneo cells altered trophoblast differentiation-related and angiogenesis-related gene mRNA expression, which also occurred in the tissues of missed and threatened miscarriage. CONCLUSIONS: SLIT2/ROBO1 signalling may regulate trophoblast differentiation and invasion causing restricting ß-hCG production, shallow trophoblast invasion and inhibiting placental angiogenesis in missed and threatened miscarriage during the first trimester.

[The microflora of vaginal, gutter, and intestinal bioptats of women with a threat of early miscarriage].

A complex simultaneous assessment of the microbiota (the aerobic and anaerobic links as well as the parietal and lumen components) of the gutter, vagina, and intestines of women with a pathological pregnancy was performed. In 30% of women the study revealed system dysbiotic changes. Local immune reactivity was decreased, which may be considered a provoking factor. In conclusion, complex microbiological examination makes it possible to objectivize the picture of the pathological process and its outcome. A criterion for the administration of correcting measures is offered.

Diagnóstico de la amenaza de parto prematuro / Diagnosis of preterm labour

La prematuridad está aumentando en todoel mundo y es actualmente uno de los principalesproblemas obstétricos. En la mayoría de loscasos de parto prematuro se produce previamenteun cuadro clínico de trabajo de partopretérmino. El diagnóstico clásico de esta entidadmediante la presencia de contraccionesuterinas y modificaciones cervicales clínicamentemuestra una baja capacidad diagnósticacon una alta tasa de falsos positivos. La valoraciónecográfica transvaginal y la determinaciónde fibronectina en las secreciones cervico-vaginales presentan una buena especificidady valor predictivo negativo y su incorporacióna un algoritmo diagnóstico podría ayudara diferenciar la verdadera de la falsa amenazade parto prematuro

Preterm birth have soared all over the world and is one of the top obstetric problems nowadays. Most cases of preterm delivery present clinical signs of preterm labor. Classic diagnosis of this disease by the presence of uterine contractions and clinical cervix effacement and dilatation show a low diagnostic accuracy with a high false-positive rate. Cervical ultrasound measurement and determination of fibronectin in cervico-vaginal secretions present a high especificity and negative predictive value and its inclusion in a diagnostic algorithm may help to differenciate the true from the false preterm labor (AU)

Cytohormonal evaluation of vaginal smears by phase contrast microscopy with special reference to progesterone deficiency pattern during early pregnancy as predictor of abortion.

Cytohormonal profile of unstained vaginal smears were studied under phase contrast microscope to define various cell morphologies in detail and build up of smear pattern serially in various stages of menstrual cycle and first trimester of pregnancy. The findings were correlated clinically and found comparable to Papanicolaou stained smears. The maturation index was calculated more objectively by phase contract microscopy because of the refractile appearance of the pyknotic nuclei of superficial cells. The prognostication of abortion was done by combining abnormal maturation index and the presence of syncytiotrophoblasts in vaginal smears. Under phase contrast microscope, the sensitivity of abnormal smear was 87.5%, the specificity was 95%, the positive predictive value was 96.55% and the overall accuracy was 90% as compared to positive Papanicolaou smear whose sensitivity though 93%, had low specificity of 50% only. Phase contrast study appears to offer certain distinct advantage over the conventional light microscopy for quick, comprehensive and quantitative assessment of the study material. It allows the physician to detect changes in the material obtained from the patients without detour of laboratory fixation and staining. It is technically easy as errors in interpretation due to unsatisfactory fixation, staining and artefacts are obviated. Thus phase contrast microscopy offers an alternative and easy method of cytohormonal evaluation of wet and unstained smears.

[Spontaneous uterine rupture in the 18th week of pregnancy in a primigravida patient with adenomyosis]. / Spontane Uterusruptur in der 18. Schwangerschaftswoche bei einer Primigravida mit einer ausgedehnten Adenomyose.

A 30-year-old primigravida experienced spontaneous uterine rupture at 18 weeks of gestation. The etiology for the rupture was an extensive, heavily decidualized adenomyosis. Although adenomyosis is relatively common, complications are rare.

[Significance of amniotic fluid cytokines measurement in threatened preterm labor and premature rupture of the membranes].

The purpose of this study was to elucidate the significance of measurements of cytokines in the amniotic fluid. Amniotic fluid was retrieved by transabdominal amniocentesis from 113 women in the following groups: Preterm labor (N = 58), PROM (N = 21) and term elective C/S (N = 34). Tumor necrosis factor alpha (TNF-alpha) and interleukin-1 beta (IL-1 beta), were measured with a commercially available ELISA. Interleukin-6 (IL-6) was measured by bioassay and newly developed "luminescencer EIA". 1. Amniotic fluid concentrations of TNF-alpha, IL-1 beta and IL-6 in cases of term elective C/S were 22.8 +/- 19.2 pg/ml, 8.1 +/- 5.2 pg/ml and 166.8 +/- 126.1 pg/ml, respectively. 2. Significantly higher levels of TNF-alpha, IL-1 beta, IL-6 were found among the cases who failed to respond to tocolysis (i.e. delivery within 48 hrs of amniocentesis). In contrast, no significant difference in such conventional markers of infection as maternal serum CRP was noted. 3. According to the degree of histopathologic chorioamnionitis (Blanc), significantly higher concentrations of IL-1 beta, IL-6 were found among the of stage III cases than those in stage II irrespective of the rupture of the membranes (IL-1 beta: 1.36 +/- 0.41 ng/ml vs 76.6 +/- 20.1 pg/ml, IL-6: 31.98 +/- 4.55 ng/ml vs 5.22 +/- 0.92 ng/ml). Significant correlation was also found between the concentrations of IL-1 beta, IL-6 and the pathological degree of funitis (Nakayama, stage 0 < stage I, stage II < stage III).(ABSTRACT TRUNCATED AT 250 WORDS)

[Morphology of the chorion based on biopsy in threatened spontaneous abortion]. / Morfologiia khoriona pri ugroze samoproizvol'nogo preryvaniia beremennosti po dannym biopsii.

70 chorion biopsies (CB) were studied morphologically under the conditions of a spontaneous abortion. Within the first trimester of the pregnancy the diagnosis of progressing, regressing and non-perspective pregnancy proved possible. The comparison of the histological examination of biopsies, endometrium scrapes and placenta with clinico-biochemical results indicates an important diagnostical and prognostical value of CB helpful in choosing corrective therapy for conservation of the pregnancy under a favourable prognosis.

[Generalized herpes in a pregnant patient]. / Generalizovannyi gerpes u beremennoi.

A clinical description of generalized herpes in a pregnant patient is presented. Virological and serological studies have confirmed the diagnosis.

Ultrasound and circulating placental protein measurements in complications of early pregnancy.

Maternal serum levels of human chorionic gonadotrophin (hCG), Schwangerschaftsprotein 1 (SP1) and pregnancy-associated plasma protein A (PAPP-A) were measured in an unselected group of 624 women presenting with amenorrhoea and vaginal bleeding with or without abdominal pain to an emergency gynaecological ultrasound clinic. Abdominal sector scanning was used to assess uterine contents. Pregnancy was confirmed by ultrasound in 406 pregnancies. Histological confirmation was obtained in each case of pregnancy failure. A live fetus was demonstrated in 259 women of whom six subsequently miscarried; one of these had markedly depressed serum hCG and PAPP-A, but normal SP1 levels, and two had oligohydramnios. Of the 147 women without ultrasound evidence of fetal heart action 67 had a correct ultrasound diagnosis of anembryonic pregnancy. The predictive value of a depressed serum hCG level was 70% in this group, and 31% in samples taken at less than or equal to 7 weeks. The predictive value of a normal hCG level was 96%. In 34 women missed miscarriage was diagnosed readily by ultrasound; all but five had depressed hCG and PAPP-A levels. A clinical diagnosis of a complete or incomplete miscarriage was made in 45 women and easily confirmed by ultrasound. All of them had depressed hCG, SP1 and PAPP-A levels. These results indicate that the diagnostic value of ultrasound in threatened miscarriage is often better than that of biochemical tests.

Histologic and immunologic study of uterine biopsy tissue of women with incipient abortion.

Biopsy specimens taken from the region of the placental bed were examined for the presence of phloxinophilic granulated mononuclear cells in women with a history of recurrent miscarriage and who would eventually miscarry a current pregnancy. They were compared with biopsy specimens from women with intact pregnancies presenting for elective termination of pregnancy and those with "missed abortion." Cells with large cytoplasmic granules (greater than or equal to 1 micron) were abundant in the group of ongoing pregnancies whereas cells with smaller granules (less than 1 micron) that were similar to large granular lymphocytes were more abundant relative to cells with large granules in the biopsy specimens from failing pregnancies. Immunosuppressive activity was tested in the supernatants of cultured biopsy samples of each group and found to be significantly lower in the incipient miscarriage group. These findings could represent alterations associated with the process of miscarriage, such as inflammation, or there may be deficient suppressor cell activity at the fetomaternal interface as the reason for "rejection" of the early embryo.

[Pathomorphology and ultrastructure of the placenta in abortion]. / Patomorfologiia i ul'trastruktura platsenty pri nevynashivanii beremennosti.

Pathologic background has been evaluated for premature delivery of 38-39, 30-37 and 20-27 week fetuses. The trial involved 115 placentas in abortion and 60 control cases of normal pregnancy. A combination of modern techniques involving histological, enzymatic and chemical has been employed as well as light microscopy. The destructive, compensatory and adjustment processes observed in the placentas were correlated topographically. The parameters registered were compared to clinical and laboratory findings. The structural basis has been defined for compensatory alterations in the placenta and pathomorphological criteria have been derived for progressive functional insufficiency at various gestation periods.