Comparison of outpatient with inpatient mifepristone usage for cervical ripening: A randomised controlled trial.

Purpose: The efficacy and safety of using mifepristone for the preinduction/induction of labour (IOL) as the only method or in combination with others has been confirmed in observational and randomised trials. However, there are currently no studies comparing the efficacy and safety of using mifepristone for the preinduction of labour on an inpatient and outpatient basis. Objective: To evaluate whether the outpatient use of mifepristone for cervical ripening before IOL at term is as efficient and safe as in inpatients. Study design: This open-label, prospective, two-arm, non-inferiority randomised controlled trial (ISRCTN26164110) with a 1:1 allocation ratio was conducted in a single tertiary referral hospital. Overall, 322 pregnant women (gestational age: 39-41 weeks; Bishop score < 6, intact membranes, no contraindications for vaginal delivery, and no contraindications for IOL) were included and randomised:162 to the outpatient group and 160 to the inpatient group for cervical ripening with mifepristone. Analyses were performed based on the intention-to-treat principle. Results: In 16 % and 17 % of the cases, labour began spontaneously within 24-36 h after taking mifepristone tablets. The additional use of prostaglandin E2 or a balloon for cervical ripening occurred equally often in the compared groups. Oxytocin was used more frequently to induce labour in the inpatient group (P = 0.035). There was no difference in the length of the interval from the onset of cervical ripening to the onset of labour between the groups (38.6 vs. 38.8 h, P = 0.900). The failed induction rate was 1.85 % vs. 0.63 % (P = 0.346).Regional analgesia (P = 0.011) and abnormal foetal heart rate patterns (P = 0.027) were more common in the inpatient group. In the outpatient mifepristone preinduction group, the average time interval from hospitalisation to discharge was 25 h shorter (P < 0.001). No statistically significant differences were observed between the groups in terms of the rates of adverse side effects or perinatal outcomes. Conclusion: Outpatient cervical ripening with mifepristone reduced the hospital stay duration compared to inpatient ripening, with no difference in efficacy in terms of improvement in the Bishop score, frequency of additional induction method usage, interval from start of preinduction to onset of labour, and labour duration.No differences in the delivery methods, failure rates, or perinatal outcomes were observed. The frequency of adverse effects was low and not related to the setting of the preinduction site. Cervical ripening with mifepristone can be performed on an outpatient basis, because it is as effective and safe as inpatient ripening.

Regulation of the Placental Renin-Angiotensin-Aldosterone System in Early- and Late-Onset Preeclampsia.

Preeclampsia (PE) is one of the most dangerous complications of pregnancy, characterized by hypertension, proteinuria, and symptoms of multiple organ failure, which are detected de novo after 20 weeks of pregnancy. The renin-angiotensin-aldosterone system (RAAS) is one of the first to recognize pregnancy and is an important regulator of blood pressure. The placenta has its own RAAS, the role of which in the development of PE is not fully understood. In this work, for the first time, we characterized the expression of RAAS components and miRNAs controlling it in the placenta at various times of PE manifestation. The data obtained will allow the development of a new strategy in the future for the search for therapeutic agents for patients suffering from PE and cardiovascular diseases.

Content of Free Fetal DNA in Maternal Blood and Expression of DNA Recognition Receptors ZBP-1 in Placental Tissue in Preeclampsia and Preterm Labor.

We evaluated the content of cell-free fetal DNA in maternal blood and expression of ZBP-1 receptors in the placental tissue of women with uncomplicated pregnancy, preeclampsia, and preterm labor. The study included 16 women with preeclampsia (early and late-onset preeclampsia, 8 cases each), 16 women with preterm labor, and 21 women with uncomplicated pregnancy. The concentration of cell-free fetal DNA was measured by PCR by detecting hypermethylated region of the RASSF1A gene. Immunohistochemistry was performed on paraffin-embedded sections of the placenta samples using primary polyclonal antibodies to ZBP-1. Significant increase in the level of cell-free fetal DNA was found in women with preeclampsia (both early and late-onset form) in comparison with uncomplicated pregnancy. The concentration of cell-free fetal DNA in preterm labor group did not differ from the control group; however, it was significantly lower than in early-onset preeclampsia, but not late preeclampsia. Immunohistochemical study showed higher expression of ZBP-1 in the villus syncytiotrophoblast in early-onset preeclampsia in comparison with that in preterm labor group (p=0.006). Fragments of damaged placental cells, predominantly trophoblast, enter maternal circulation and are the source of cell-free fetal DNA and a potential ligand for ZBP-1, which leads to further cell damage and the formation of a vicious circle. The increase in the content of cell-free fetal DNA in maternal blood and ZBP-1 expression in the syncytiotrophoblast in preeclampsia are interrelated processes reflecting impaired morphofunctional state of the placenta.

Correction to: Abstracts : 30th European Congress of Pathology.

In Poster Sessions, the author name G. Khlestova was incorrectly presented as 'K. Galina' in the authorship group for Abstract PS-18-017 (page S151). The name has been corrected in the authorship group shown above.

Dynamics of Renin, Angiotensin II, and Angiotensin (1-7) during Pregnancy and Predisposition to Hypertension-Associated Complications.

Changes in the levels of rennin, angiotensin II, and angiotensin (1-7) were studied during normal pregnancy. The blood was taken on gestation days 140-237 and 238-280. No significant changes in renin concentration were observed during normal pregnancy (p=0.423). The level of angiotensin II increased during normal pregnancy from 9.7±1.2 to 14.7±1.9 pg/ml (p=0.019). On the contrary, angiotensin (1-7) concentration decreased from 771.1±44.2 to 390.7±13.9 pg/ml (p<0.001). The shift in the proportion between vasoconstrictor angiotensin II and vasodilaltor angiotensin (1-7) attests to high predisposition of pregnant women to hypertension-related complications.

DAI-1 Receptor Expression in Placenta in Earlyand Late-Onset Preeclampsia.

DAI-1 receptor (DNA-dependent activator of IFN-regulatory factors; DLM-1/ZBP-1) is an innate immunity cytoplasmic receptor of the DNA-recognition receptor class of antiviral immunity. DAI-1 expression reflects the severity of the inflammatory response that plays the key role in the pathogenesis of pregnancy complications. We studied DAI-1 receptor expression in the placental villi in early- and late-onset preeclampsia. In case of early-onset preeclampsia DAI-1 staining intensity was lower (p=0.01), and in case of late preeclampsia - significantly higher (p<0.005) than in the reference groups at the corresponding gestational age. There was revealed a correlation between the decrease in DAI-1 receptor expression and the severity of disease progression.

[Morphological Features of Mesenhymal Stroma Cells of Chorionic Villi].

Background: Nowadays autologous mesenchymal placental stromal cells (MSCs) may use to treat for various diseases both of the mother and the child. Stroma of the placenta villi is appropriated origin for cell culture isolation. Aim: of the study was to evaluate the possibility for selection and use of placental tissue for mesenchymal stromal cells. Materials and methods: The present study was based on 45 placental samples of women aged 27−38 yy. who underwent surgical delivery at 36−40 weeks of gestation. 30 of these women have been enrolled in the basic group including children with congenital abnormalities (CA). The comparison group consisted of 15 patients with physiological pregnancy. We performed histological examination (with hematoxylin and eosin staining), immunohistochemical examination (with use monoclonal antibodies CD90 (1:25; Abcam, UK), СD105 (1:500; Abcam, UK), CD44 (1:25; Dako), СD73 (1:200, Abcam, UK), and electron microscopy (by microscope Philips/FEI Corporation, Eindhoven, Holland). Eclipse 80i microscope (Nikon Corporation, Japan) was used to examine the immunohistochemical reactions as a brown staining. The evaluation of the intensity of reaction was conducted by NIS-Elements Advanced Research 3.2 program (Czech Republic). Student's t-test and analysis of variance were used to compare the mean values. Differences were considered statistically significant at p<0.05. Results: Interstitial cells of the stroma of the villi with CA had fibroblastic differentiation as revealed degenerative changes of the cells. The histologic examination with hematoxylin and eosin staining revealed significant fibrosis of the stroma of the placenta villi in CA group (p<0,01). Immunohistochemical study of stem and intermediate chorionic villi revealed no significant differences in staining of CD44+, СD90+, СD73+, and CD105+ cells if compared to the control group (p>0.05). Although CD105 expression was significantly lower in the CA group (0.058±0.0049) than in the control group (0.088±0.0039) (p<0.05). However, electron microscopy detected the villi interstitial stromal cells with fibroblastic differentiation in CA group. Conclusions: Thus, it is necessary to exclude placenta with obstetrical history, somatic, and congenital pathology of the mother and the child when selecting the placental cell culture. Moreover, choosing a sample the morphological structure of the placenta should be taken into consideration. However, congenital malformations of the fetus, pathology of the mother cultivate mesenchymal stromal cells of placentas is inappropriate and should be taken advantage of the donor cells.

Caspase expression in placental terminal villi in spontaneous and induced pregnancy.

Placental levels of caspase 1, 8, and 10 were studied by the immunohistochemical method in full-term spontaneous and induced pregnancies. The levels of these caspases in the placental terminal villi were significantly higher in induced pregnancy. The changes were more marked after intracytoplasmatic injection of spermatozoa.

Expression of carbohydrate metabolism markers in full-term spontaneous and induced pregnancy.

Peculiarities of the expression of glucose transporter (GLUT1 and GLUT3) and insulin-like growth factor immunophenotypes in placental villi in full-term physiological pregnancy were studied by immunohistochemical method. In induced pregnancy, changes of different degree in the expression of carbohydrate metabolism markers were detected (most pronounced changes were detected in GLUT3 expression), which was probably associated with higher incidence of obstetrician complications in these patients.

Markers of transmembrane and energy exchange in cells of terminal placental villi in spontaneous and induced pregnancy.

We performed a comparative morphological study of the placentas in spontaneous and induced pregnancy. Immunohistochemical analysis revealed pronounced decrease in the expression of markers of transmembrane (α-SNAP 23, annexin 3) and energy (ferritin light chain, ATP5J) in placental terminal villi.

Peroxisome proliferator-activated receptors of trophoblast cells in miscarriage.

Comparative histological study of uterine curettage specimens in missed abortion in women with spontaneous and induced pregnancy and progressing spontaneous pregnancy revealed similar changes in the endometrium and placental villi. Immunohistochemical assay showed enhanced expression of PPARγ and increased proliferation index (Ki-67) in cells of the villous and extravillous trophoblasts in missed abortion.

[Clinical significance of examinations of hemodynamics of mother and fetus in physiological and complicated pregnancy]. / Klinicheskoe znachenie issledovaniia gemodinamiki materi i ploda pri fiziologicheskoi i oslozhnennoi beremennosti.

Summarized in the paper is the experience of defining the clinical significance of examination of hemodynamics of mother and fetus in physiological and complicated pregnancy. The normative parameters of blood circulation in the vessels of mother and their central hemodynamics are described. An interrelation between the changes of central hemodynamics of mother and fetus are shown in the development of gestosis and placental insufficiency. The orientation, succession and changes of blood circulation in the arteries and venous vessels of fetus are demonstrated in chromosomal anomalies, congenital malformation, premature pregnancy, gestosis, fetoplacental insufficiency and postmaturity. It was proven as prognostically valuable to study the parameters of blood circulation of mother and fetus not only in diagnostically complicated pregnancy but also in evaluating the therapy efficiency, as well as in choosing a method and time for delivery and in prognosticating a perinatal outcome.

[Current diagnostic methods and therapeutic principles in various forms of puerperal endometritis]. / Sovremennye metody diagnostiki i printsipy terapii razlichnykh form poslerodovogo éndometrita.

A total of 55 puerperants+ with endometritis followed by spontaneous labours (26 females) and cesarean operation (29 females) were studied. A comprehensive study involved echography, hysteroscopy, bacteriological analysis of the uterine content, and histological examination of mucosal curettage of the corpus uteri. Three types of the clinical course of endometritis were identified: 1) in the presence of placental tissue residues; 2) with necrosis of delayed decidual tissue and lochia- or hematometra; and 3) a "pure" type of endometritis without abnormal tissues in the uterus. Uterine curettage was performed in the first type of endometritis, vacuum aspiration of its content was carried out in Type 2. The patients from Group 3 who had the most severe inflammatory process of the uterus underwent its cavity washing with large volumes of cold antiseptic solutions, took detoxifying, ++rheo-vasoactive and protein agents, received immunomodulating and uterotonic therapy. The algorithm developed for management of puerperants+ with postpartum endometritis substantially enhanced the efficiency of therapy and prevented severe septic events in time.