Community acceptability of contraception after induced versus spontaneous miscarriage.

Objective: To study the relationship between history of miscarriage (induced or spontaneous) and current use of modern contraceptive method among women in Pakistan. Study Design: Cross Sectional study. Setting: OPD of MCH, PIMS. Period: July 2019 to December 2019. Material & Methods: A total of 80 married women were enrolled, 40 women who had induced miscarriage (group A) and 40 from spontaneous miscarriage (group B). Data is obtained on predesigned questionnaire. Primary outcome was acceptance of contraception (LARC) after induced versus spontaneous miscarriage. Results: About 51% of women were in the age group of 30–35 years and out of total 80 women, 67 (83%) women had parity of three or above (27 % had parity of three). Out of 66 women who used contraception, 35 (53%) had induced miscarriage (group A) and 31 (46%) had spontaneous miscarriage (group B). Women who belonged to induced miscarriage (group A) faced menstrual irregularity, as the reason of leaving contraception, followed by chronic PID and husband opposition. While in the group B, fertility desire was main reason of discontinuation of contraception. In Group A, 20 (50%) women were willing to use LARC (long acting reversible contraception) after induced abortion to reduce the chances of unwanted pregnancy while in other group B, 15 (37.5%) women were wanted to use LARC and 18 (45%) women were not ready to use contraception due to fertility. Conclusion: High rate of induced abortion due to failed contraception and dis-continuation of contraceptives needs to be addressed by encouraging women to manage the side effects to ensure continuity of contraceptives.

Features of Microbiocenoses of Various Biotopes in Women as Potential Miscarriage Risk Factor

Relevance. Miscarriage is one of the most common obstetric pathologies that determine the spontaneous death of the fetus. The role of changes in the microbiome of various biotopes is considered as a risk factor of this disease.Aim of the research is to assess the microbiocenoses structure of the reproductive system and the intestine associated with the development of spontaneous miscarriages in early pregnancy.Materials and methods. A case-control study was conducted and organized. The group of «cases» included 23 women with spontaneous miscarriage at 5–14 weeks of pregnancy and the control group included 23 women with normal pregnancies Based on the data of metagenomic sequencing of V3–V4 regions of the 16S rRNA gene, a comparative assessment of the structure of the vaginal and intestinal microbiome in these groups was carried out.Results. As a result of the study, a number of taxonomic groups of microorganisms in the vagina and intestines associated with miscarriage. It was found that the decrease in the proportion of Lactobacillus spp. in the structure of the vaginal microbiome, less than 90% of the total number of identified taxa is associated with this pathology (OR = 5.28 (95% CI = 1.2-23.2)). The gut microbiocenoses of women with spontaneous miscarriage are characterized by less taxonomic diversity than the gut microbiome of women with advanced pregnancy. At the same time, some representatives of the intestinal microbiome (Akkermansia sp., Faecalibacterium sp., Bifidobacterium sp., Methanobrevibacter sp., Lactococcus sp.) predominate in women with a normal pregnancy.Conclusion. The study demonstrated a significant role of changes in microbiocinosis of the reproductive tract and intestines in miscarriage. There is a potentially protective function of lactobacilli. The obtained data substantiates the need for active use of molecular genetic methods focused on the assessing the structure of the vaginal and intestinal microbiota in assessing the risks of reproductive failures.

REGULATION OF PERIPHERAL B-LYMPHOCYTE DIFFERENTIATION IN RECURRENT MISCARRIAGE

The important role of immune disorders in recurrent miscarriage has been proven. Clarification of the character of B-lymphocyte differentiation and its regulation factors in women with threatened miscarriage and recurrent miscarriage in history is an urgent problem, since it will reveal the immune mechanisms of the pathogenesis of this pathology. Purpose: to establish the features of B-lymphocyte differentiation and factors of its regulation in women with a history of recurrent miscarriage and threatening spontaneous miscarriage at the time of examination.Were examined pregnant women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 60 pregnant women with a threatening spontaneous miscarriage at the time of examination and a history of recurrent miscarriage. As a control, 35 pregnant women with uncomplicated pregnancy were examined. The comparison group consisted of 25 primary pregnant women with threatened spontaneous miscarriage at the time of examination. The material for the study was peripheral venous blood. Subpopulations of B-lymphocytes CD19+, CD19+ IgD+, CD20+IgM+, CD20+IgG+ were determined by flow cytometry; CD19+CD20- CD38+, CD19+CD27- , CD19+CD27+. Serum levels of BAFF and APRIL were assessed by enzyme-linked immunosorbent assay.In the main group, an increase in the proportion of B-cells, CD20+IgM+-lymphocytes and memory cells was recorded in the peripheral blood, along with a decrease in the level of naive cells and plasma cells. In the comparison group, an increase in the proportion of immature IgM+B-cells, circulating memory cells, along with a decrease in naive B-lymphocytes, was registered. in the main group there was a pronounced decrease in the serum BAFF level compared with the control and comparison groups. Analysis of the APRIL content showed a pronounced downward trend in groups with threatened miscarriage relative to healthy pregnant women. Thus, threatening habitual and sporadic miscarriages were associated with a shift in the differentiation of B-lymphocytes towards immature forms and a lack of regulatory influence of BAFF and APRIL, which is reflected in the disruption of B-cell homeostasis and weakening of humoral effector mechanisms at the systemic level. The revealed changes may indicate a single mechanism for the development of a threatening spontaneous miscarriage, the severity of which increases with repeated loss of pregnancy. These changes can lead to an increase in effector cytotoxic mechanisms and an increase in proinflammatory cytokines, which can lead to the development of damaging reactions in the fetoplacental complex, which can be reflected in the clinical picture of the threat of termination of pregnancy.

FEATURES OF MONOCYTE POLARIZATION AT DIFFERENT OUTCOMES IN WOMEN WITH RECURRENT MISCARRIAGE

Currently, in the pathogenesis of recurrent miscarriage, a special role is given to immunological factors, in particular the role of innate immunity. The aim of the study was to assess the relative content of monocytes in the peripheral blood producing IL-4, IL-6, IL-10, IFNγ, as well as to identify new criteria for predicting the outcome of pregnancy in women with the threat of early termination and recurrent miscarriage. Materials and methods. 88 pregnant women at 5-12 weeks’ gestation were examined, the main group consisted of 59 women with recurrent miscarriage and threatened miscarriage at the time of the study, the control group – 29 women with uncomplicated pregnancy without recurrent miscarriage. The main group, depending on the outcomes of pregnancy, was subdivided into subgroups: subgroup I – 42 women whose pregnancy ended in timely delivery, subgroup II – 8 women with preterm labor, subgroup III – 9 women with abortion up to 22 weeks (spontaneous miscarriage and non-developing pregnancy). In the control group, all women had a timely delivery. Research material – peripheral venous blood. The relative content of IL-4+, IL-6+, IL-10+, IFNγ+ monocytes was assessed on a FACSCanto II flow cytometer using monoclonal antibodies. Statistical data processing was carried out using a package of standard applied programs. Results. In the group of women with recurrent miscarriage and threatened miscarriage, the relative content of IL-10+ and IL-4+ monocytes was reduced and the content of IL-6+ monocytes was increased compared to the control group (p = 0.0001 in all cases). There were no statistically significant differences in the content of IFNγ+ monocytes in the compared groups (p = 0.069). With a relative content of IL-4+ monocytes equal to 26.7% or less, preterm labor is predicted. With a relative content of IL-10+ monocytes equal to 27.0% or less, abortion (spontaneous miscarriage or miscarriage) is predicted in gestational age up to 22 weeks. An increase in the ratio of IFNγ+/ IL-4+, IFNγ+/IL-10+, IL-6+/IL-4+, IL-6+/IL-10+ monocytes was found in the main group (p < 0.0001 in all cases ). Conclusions. In women with recurrent miscarriage in all subgroups, the level of M1 monocytes prevailed over the level of M2 monocytes. The data obtained allowed the development of new prognostic criteria for termination of pregnancy up to 22 weeks and premature birth.

Regulation of the functional activity of peripheral B lymphocytes in pregnant women with a history of recurrent miscarriage

BACKGROUND:The frequency of recurrent miscarriage is up to 5 % of all desired pregnancies and is mainly due to immunological disorders. Dysfunction in the regulation of the functional activity of B lymphocytes is the pathogenetic link in multiple obstetric complications, including habitual miscarriage. AIM:The aim of this study was to characterize the regulation of the functional activity of peripheral B lymphocytes in pregnant women with threatened spontaneous miscarriage and a history of habitual miscarriage. MATERIALS AND METHODS:We examined 88 women aged 18-40 years at a gestation period of 5-12 weeks. The main group consisted of 36 patients with threatened spontaneous miscarriage at the time of examination and a history of habitual miscarriage. The control group included 28 women with uncomplicated pregnancy. The comparison group consisted of 24 primary pregnant patients with threatened spontaneous abortion at the time of examination. BAFF and APRIL levels in the blood serum were determined by enzyme immunoassay. The content of CD19+BAFFR+B lymphocytes in the lymphocyte gate was evaluated in the peripheral blood by flow cytometry using monoclonal antibodies. Akt mRNA expression was assessed using real-time reverse-transcription quantitative polymerase chain reaction. CD19+В lymphocytes were isolated by direct magnetic separation. RESULTS:In the main group, there was an increase in expression of BAFF receptors on peripheral CD19+B lymphocytes and a decrease in the serum BAFF concentration compared to the parameters in the other study groups. We also found a pronounced trend towards a decrease in the serum APRIL level in the main and comparison groups of patients compared to healthy pregnant women. Besides, Akt mRNA expression in peripheral CD19+B lymphocytes was increased in the main group. CONCLUSIONS:Threatened habitual abortion is associated with the deficit of the regulatory influence of BAFF and APRIL, which is expressed in the disruption of B cell homeostasis and the weakening of humoral effector mechanisms.

Spontaneous Miscarriage in Women Having More Than Three Miscarriages and Advanced Maternal Age

Background: Miscarriages are negative outcomes of a pregnancy. Their ratio increases in women with recurrent miscarriages. Objective: To identify the role of age and recurrent miscarriages in spontaneous abortions. Study Design: Comparative analytical study Place and Duration of Study: Department of Obstetrics & Gynecology, Mohtarma Benazir Bhutto Medical College Mir Pur, Azad Kashmir from 1st October 2020 to 31st March 2021. Methodology: One hundred and twenty pregnant women between the age group of 19-40 years. The clinical history of recurrent miscarriages and demography was noted. Results: The mean age was 29.85±4.71 years with 42% of previous miscarriage occurred in pregnant women at their first trimester. The highest number of recurrent miscarriages (>4) was noted in 36-40 years of age group. Conclusion: The rate spontaneous miscarriages increases with increasing age and recurrent history of miscarriages Key words: Spontaneous miscarriage, Advanced maternal age, Recurrent

Role of CD20 + IL-10 + B-lymphocytes in immunoregulatory processes in women with reccurent miscarriage

To determine the level of CD20 + IL-10 + B-lymphocytes in pregnant women with the threat of termination of pregnancy at 5-12 weeks and recurrent miscarriage in history and compare the data obtained with the end of gestation. A survey of 65 women at a gestational age of 5-12 weeks was carried out. The main group consisted of 33 women with a threatening recurrent miscarriage at the time of the examination, the comparison group consisted of 10 pre-pregnant women with a threatening sporadic miscarriage at the time of the examination, the control group consisted of 22 pregnant women without signs of a threatening miscarriage. The main group, depending on the outcomes of pregnancy, is divided into 2 subgroups: subgroup A - pregnancy ended in undeveloped pregnancy or miscarriage (9 women), subgroup B - pregnancy ended in childbirth (24 women). The relative content of CD20 + IL-10 + B-lymphocytes was determined by flow cytometry on FACSCanto II (Becton Dickinson, USA). Women in the main group had a significantly lower level of CD20 + IL-10 + B-lymphocytes in comparison with the rest of the surveyed. A retrospective analysis revealed that among women of subgroup A there was a sharp decrease in CD20 + IL-10 + cells compared with subgroup B. Prediction of a non-developing pregnancy and spontaneous miscarriage up to 22 weeks of gestation in pregnant women with threatened spontaneous miscarriage and a history of recurrent miscarriage is possible with the relative content of CD20 + IL-10 + equal to or less than 4.5% (sensitivity 100%, specificity 82.6%, accuracy 87.9%).