Spontaneous Termination Of Pregnancy Research Articles

Abnormal methylation of PRDM16 and PTPRN2 genes in chorionic villi in miscarriage

Relevance. Abnormal epigenetic regulation of genes responsible for the development of the embryo and placenta is associated with many pregnancy pathologies. Aim. The aim of this work was to analyze the prevalence of abnormal methylation of the PRDM16 and PTPRN2 genes in chorionic villi of spontaneous abortions with normal karyotype and with the most frequent aneuploidies (trisomy 16 and monosomy X). Materials and Methods. The methylation profile was evaluated using targeted bisulfite massive parallel sequencing in chorionic villi of induced abortions (n = 10), spontaneous abortions with normal karyotype (n = 39), trisomy 16 (n = 17) and monosomy X (n = 20) and peripheral blood lymphocytes of healthy volunteers (n = 6). Results and Discussion. In analyzed genes, differential methylation of individual CpG sites was found in chorionic villi of spontaneous abortions. Despite the absence of significant differences between the groups in the average level of methylation in analyzed gene regions, abnormal methylation of the PRDM16 and PTPRN2 genes were detected for 33 % and 5 % of spontaneous abortions, respectively, indicating a high incidence of epigenetic abnormalities in these genes in the chorionic villi of spontaneous abortions. The level of methylation of the PRDM16 gene significantly correlated with the level of methylation of the retrotransposon LINE-1, which indicates the generalized nature of methylation disorders in spontaneous abortions. Finally, the level of methylation of the PTPRN2 gene depended on the age of mothers of spontaneous abortions with monosomy X, which raises the question of the influence of maternal factors on the methylation profile in this group of spontaneous abortions. Conclusion. The results indicate that epigenetic disorders of the PRDM16 gene may be associated with spontaneous termination of pregnancy in the first trimester.

Repair of the reproductive function of the endometrium after hysteroscopic myomectomy

The aim. To reduce the frequency of reproductive function disorders and preserve fertility in women after conservative myomectomy by developing and implementing a complex of rehabilitation measures into clinical practice.
 Materials and Methods. The study involved 301 women of reproductive age (221 with a diagnosis of submucosal uterine fibroid (UF)), who were divided into groups: 1 Group - 121 people who used the proposed postoperative rehabilitation therapy; Group 2 - 100 women operated on for submucous uterine fibroids, but without the use of restorative therapy, Group 3 C (control) - 80 somatically and gynecologically healthy women of reproductive age. Depending on the clinical assessment of the complexity of hysteroscopic resection of the node, hysteroscopy or laparoscopy was performed (according to FIGO recommendations). Clinical, instrumental, and laboratory research methods and methods of statistical analysis were used.
 Results. The main risk factors for the development of submucosal UF are a combination of interdependent factors - genital endocrine-dependent pathological processes (64%) and chronic inflammation of the endometrium on the background of its traumatization - during abortions or directly by a submucosal node (36%). The obtained results made it possible to substantiate pathogenetically the need to improve the scheme of treatment and rehabilitation therapy for women with submucosal leiomyoma of the uterus in the postoperative period in order to preserve reproductive function, which included drugs with antiproliferative, anti-inflammatory, immunomodulating, NO-donor and angioprotective effects. The proposed scheme of treatment and rehabilitation measures is based on a pathogenetic orientation, which allows obtaining a long-term antiproliferative effect on the endometrium and makes it possible to normalize the hormonal relationships and receptor status of the endometrium without the appointment of long-term traditional progestogen-estrogen monotherapy, makes it possible to restore the processes of synchronization of proliferation /transformation of the endometrium to the follicular and luteal phases of the menstrual cycle with the formation of the window of implantation, which contributes to the onset of pregnancy. Thus, in the operated women of the 1 Group, pregnancy after hysteroscopic myomectomy occurred in 15% after 6 months, after a year - in 22%, after one and a half - in 45%, which ended in childbirth through the natural birth canal - in 48%, by cesarean section in 34.5% of people, and 18% had premature births, 10% had spontaneous termination of pregnancy. Accordingly, in the 2 Group (without the proposed therapy) the following data were observed: pregnancy after 6 months in 12%, after a year in 20%, after one and a half - in 40%, which ended in childbirth through natural birth canals - in 40%, by cesarean section in 30.5% of people, and in 17.5% there was a premature birth, in 12% - spontaneous termination of pregnancy occurred.
 Conclusions. The clinical effectiveness of using the proposed, developed, and improved scheme of treatment and rehabilitation therapy within 6 months was 35.1% in the main group compared to 15.4% in women of the comparison group (without therapy).

Restoration Treatment for Female Patients with Non-Bearing Pregnancy at the Early Terms of Gestatione

An important indicator of reproductive health is pregnancy failure, which has no decreasing trend worldwide [1-3]. Despite certain successes achieved in treatment and rehabilitation, the problem of pregnancy failure, especially in early gestation, is still urgent [4-6]. Thus, according to different authors, it ranges from 2 to 55%, reaching up to 80% in the first trimester. Statistically, 15 to 25% of all registered pregnancies are spontaneously miscarried, and 80% of pregnancies are terminated before 12 weeks of gestation. The incidence of spontaneous miscarriage remains consistently high, at 45-88.6% of early spontaneous miscarriages. Direct reproductive losses from non-pregnancy in Ukraine amount to 36-40 thousand unwanted children annually. It has been established that the state of reproductive health depends to a greater extent on the duration of pregnancy failure and the complex of rehabilitation measures [1-3]. When a pregnancy occurs within the first 6 months, after a previous miscarriage, a large number of repeated pregnancy losses have been noted. The rate of pregnancy loss after a single miscarriage is 13-17%, after two miscarriages 36-38%, and with recurrent miscarriage up to 45% [1-3]. After spontaneous abortion it is necessary to rehabilitate a woman's reproductive health regardless of the number of spontaneous miscarriages, taking into account all the causes and conditions that contribute to spontaneous pregnancy termination. The principles of the reproductive health rehabilitation program for women after spontaneous miscarriage include the earliest possible initiation of treatment and rehabilitation measures, the principle of an individual approach to rehabilitation measures for each patient [4-6]. The principle of dynamic control over the effectiveness of rehabilitation and therapeutic measures and the principle of continuity between inpatient, outpatient, and sanatoriumresort units of rehabilitation measures are important when using the methods and means of physical rehabilitation [4-7].

Women’s Mental Health and Pregnancy Loss: What Should We Be Aware Of?

IntroductionPregnancy loss (PL) – by induced or spontaneous termination of pregnancy – is common, although its consequences on women’s mental health are often neglected in clinical practice.ObjectivesTo understand the existence of psychiatric morbidity in women, associated with PL, as well as related risk factors.MethodsNon-systematic review of literature through search on PubMed/MEDLINE for publications up to 2021, following the terms ‘pregnancy loss’, ‘psychiatry disorder’, ‘depression’ and ‘anxiety’.ResultsAfter a PL, anxiety is the most frequent symptomatology in 41% of women. Depression occurs in 22-36% of women in the first two weeks after PL, declining over time. Symptoms compatible with Post Traumatic Stress Disorder (PTSD) are found in 25% of women with PL in the first month. Women who meet criteria for PTSD are more likely to present criteria for Depressive Episode. Substance Use Disorder and Prolonged Grief Disorder are also reported, the latter having, as predictors, previous relational difficulties, poor social support and absence of descendants. Risk factors associated with significant psychopathology within PL are, for example, nulliparity, infertility, previous PL, longer gestation time, lower marital satisfaction, previous psychiatric illness, and history of abuse.ConclusionsIn clinical practice, the risk of psychopathology in women with PL should be considered. This population should be actively questioned about the presence of symptoms, as well as their persistence and impact, requiring timely and appropriate pharmacological and psychotherapeutic intervention. Perinatal Mental Health interventions show important gains in the overall health of women and their offspring.DisclosureNo significant relationships.

Optimization of the sperm processing protocol for subsequent molecular cytogenetic studies.

One of the causes of spontaneous pregnancy termination, infertility, and birth of children with development delay and malformations are chromosomal abnormalities (CA) as well as spontaneous aneuploidies in gametes of phenotypically normal parents. Often couples with reproductive problems, as well as spouses one of whom is a carrier of CA, turn to the programs of assisted reproductive technologies (ART) for preimplantation evaluation of the zygote chromosomal status. As part of ART programs, parental gametes are examined to assess the level of spontaneous aneuploidy. As a rule, the most accessible material for analysis is the ejaculate. Fluorescent in situ hybridization (FISH) is used to examine male gametes obtained from the ejaculate. However, this FISH-analysis has a number of limitations and difficulties because of the peculiarities of the sperm head structure, namely the supercondensed state of chromosome chromatin. In order to optimize the FISH protocol, five different protocols were used for pre-hybridization processing of ejaculate samples obtained from nine phenotypically normal men. A comparative analysis of hybridization efficiency showed that the protocol using tris(2-carboxyethyl)phosphine hydrochloride (TCEP) as a decondensation agent was the most effective for subsequent molecular cytogenetic studies. The developed hybrid protocol combining proteolytic pretreatment, TCEP and thermal decondensation can be used when other protocols for pre-hybridization treatment of ejaculate preparations are not effective.

ОПЫТ УСПЕШНОЙ РЕАБИЛИТАЦИИ ПОСЛЕ САМОПРОИЗВОЛЬНОГО АБОРТА

The state of health of the child begins to form in the prenatal period and is determined by both the health of the parents and the conditions of pregnancy. In accordance with the WHO recommendations, it is possible to reduce reproductive failures by consulting women of reproductive age even before conception — at the pre-pregnancy stage, with measures aimed at reducing miscarriage and premature birth, as well as complications during pregnancy. According to the Russian clinical protocols for the management of patients after spontaneous termination of pregnancy in the early stages, a dose of folic acid 400 mcg is adequate for the prevention of neural tube defects and other fetal malformations, which often lead to early spontaneous pathological abortions. Folate is involved in the synthesis of DNA and prevents its changes by methylation, which is extremely important in rapidly dividing cells, which is characteristic of pregnancy. This is the basis for reducing the risk of miscarriage and premature birth, contributing to the normalization of the process of ovum nidation and placentation, as well as reducing the complications of gestation, the frequency of malformations in children. The purpose of this study is to prove by the example of a clinical case study that the inclusion of the active form of folate in pre-gravidar preparation is an effective way of rehabilitation after spontaneous abortion. Folate deficiency can lead to a state of hyperhomocysteinemia, leading to increased microthrombosis and changes in microcirculation, which leads to implantation defects and fetoplacental disorders. These processes may underlie the pathogenesis of miscarriage in early gestation, as well as the formation of chronic placental insufficiency and fetal growth retardation in the second half of pregnancy. Folate deficiency may be the cause of reproductive failures that are not related to other causes that cause spontaneous termination of pregnancy, as may have occurred in the clinical case we are studying.

CLINICAL-DIAGNOSTIC AND PATHOGENETIC ASPECTS OF NON-DEVELOPING PREGNANCY

The problem of miscarriage is especially relevant in modern conditions of decreasing population growth. Miscarriage is understood as the spontaneous termi-nation of pregnancy from conception to 37 weeks of gestation. It is very important to maintain the desired pregnancy, because according to statistics, every five years the number of women who are able to give birth to a child decreases by 20%, which indicates an unfa-vorable demographic situation. Despite the large number of works devoted to the problem of non-developing pregnancy, the final etiological factors, pathogenetic and clinical course of the pathology are not clearly defined. A significant place in the struc-ture of etiological factors in the development of non-developing pregnancy by scientists and clinicians is assigned to endocrinological, immunological, genetic and infectious factors, which allows us to consider this pathology as polyetiological. Since the incidence of non-developing pregnancy is quite high, it is neces-sary to conduct research to establish the etiological, pathogenetic, clinical features of the pathology, as well as to develop effective methods for the correction and prevention of this condition, which will allow during the pregravid preparation period to exclude possible risk factors and prevent the development re-duce the risks of the formation of a non-developing pregnancy.

Amniotic Membrane Seeded Fetal Fibroblasts as Skin Substitute for Wound Regeneration.

Various natural and synthetic biomaterials have been applied as skin substitutes for regenerating damaged skin. Here, we describe a straightforward method for fabrication of a tissue-engineered skin substitute by seeding human fetal fibroblasts on acellular human amniotic membrane (HAM). Fetal fibroblasts are achieved from the skin of normal and non-macerated fetus of 11-14weeks old after spontaneous pregnancy termination. Acellular HAM is obtained by separation of the outer membrane of the chorion and removing its epithelial cells.

The Role of Pro- and Antioxidant Systems in the Development of Placental Dysfunction in Human Pregnancy

The pro-and antioxidant systems of the human placenta have been studied in its central and peripheral areas in the state of dysfunction. It has been shown that the intensity of free-radical oxidation (FRO) is 24% higher (p < 0.05) in mitochondria isolated from peripheral placental areas in the case of preterm termination of pregnancy than in placental mitochondria of women with normal pregnancy ending in delivery on due dates. The values of total antioxidant activity in mitochondria isolated from the central and peripheral areas of placentae of women with preterm labor exceeded 1.5-and 1.8-fold the respective values for the placental mitochondria of women with the normal duration of pregnancy. The rate of glutathione peroxidase activity in placental mitochondria of women with preterm labor was lower than in patients with normal duration of pregnancy terminated on due dates. Higher values of intensity of both the FRO processes and the active components of thiobarbituric acid (TBA) were recorded (higher by 42% and 62%, respectively) in the postmitochondrial fraction in the peripheral area of placentae of women with spontaneous termination of pregnancy, compared with the placentae of women with uncomplicated duration of pregnancy with labor on due date. No differences have been observed in the intensity of oxidative modification of placental proteins in both the periphery and the center in the placentae of women from the studied groups. The rate of glutathione peroxidase activity in the placenta of women with spontaneous termination of pregnancy was more than twice as high as the activity of this enzyme during the first trimester of normal pregnancy and remained high during the second and third trimesters. The activity of the enzyme did not depend on its localization (center or periphery) in placentae of women participating in the study. The values of glutathione transferase activity in the placentae increased in the course of normal pregnancy but remained at the level of the first trimester in the central and peripheral areas in the case of a miscarriage at different gestational terms. Our findings allow us to suggest that oxidative stress developing in placenta from its center to periphery plays a key role in the pathogenesis of placental dysfunction, mainly, due to the glutathione-dependent component of the placental antioxidant defense.

Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure

BackgroundTrophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).MethodsThis study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).ResultsMMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.ConclusionsHuman placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Population-Based Surveillance for Neonatal Herpes in New York City, April 2006–September 2010

Population-based data for neonatal herpes simplex virus (HSV) infection are needed to describe disease burden and to develop and evaluate prevention strategies. From April 2006 to September 2010, routine population-based surveillance was conducted using mandated provider and laboratory reports of neonatal HSV diagnoses and test results for New York City resident infants aged ≤60 days. Case investigations, including provider interviews and review of infant and maternal medical charts and vital records, were performed. Hospital discharge data were analyzed and compared with surveillance data findings. Between April 2006 and September 2010, New York City neonatal HSV surveillance detected 76 cases, for an average incidence of 13.3/100,000 (1/7519) live births. Median annual incidence of neonatal HSV estimated from administrative data for 1997 to 2008 was 11.8/100,000. Among surveillance cases, 90.8% (69/76) were laboratory confirmed. Among these, 40.6% (28/69) were HSV-1; 39.1% (27/69) were HSV-2; and 20.3% (14/69) were untyped. The overall case-fatality rate was 17.1% (13/76). Five cases were detected among infants aged >42 days. In all, 80% (20/25) of the case-infants delivered by cesarean section were known to have obstetric interventions that could have increased risk of neonatal HSV transmission to the infant before delivery. Over half (68%, or 52/76) of all cases lacked timely or ideal diagnostics or treatment. Administrative data may be an adequate and relatively inexpensive source for assessing neonatal HSV burden, although they lack the detail and timeliness of surveillance. Prevention strategies should address HSV-1. Incubation periods might be longer than expected for neonatal HSV. Cesarean delivery might not be protective if preceded by invasive procedures. Provider education is needed to raise awareness of neonatal HSV and to assure appropriate testing and treatment.

Abdominal Surgery during Pregnancy: a Retrospective Study of 23 Patients

Objective : The aim of this study was to demonstrate that during pregnancy a large variety of non-gynaecological abdominal pathologies can be safely managed with surgery.Methods : The medical records of twenty-three patients that were pregnant and underwent open or laparoscopic surgery from 1997 to 2007 were reviewed.Results : Twenty-one of the 23 patients have given birth and all but one of the babies were healthy with normal weights, sizes, and APGAR scores. One patient had spontaneous termination of pregnancy one week after the surgical procedure and one patient is out of follow-up. Preterm partus was induced in three patients due to life-threatening conditions for the mother. Each laparoscopy was performed safely without peri-operative complications. Conclusion : Open or laparoscopic abdominal surgery poses little or no additional risk for mother or child.

Functional ismico-cervical insufficiency and its therapy with dufastone in outpatient settings

The role of ischemic-duodenal insufficiency (IDI) in spontaneous termination of pregnancy has not been fully elucidated. The development of various modifications of the surgical treatment of IDI is of great importance, which has led to a very wide use of surgical interventions on the cervix, including "prophylactic" interventions. The application of a circular suture to the cervix is appropriate only in cases where there is an organic variant of this pathology. Differential diagnosis of organic and functional IDI in pregnancy is difficult.