Comparative study of mifepristone followed by misoprostol with misoprostol alone for treatment of early pregnancy failure: an interventional randomised clinical study in a tertiary care hospital

Background: Early pregnancy failure (EPF) is a common experience for women. Medical management allows for expulsion of the nonviable pregnancy in a controlled manner without any surgical risk. The aim of this study was to compare efficacy and safety of mifepristone followed by misoprostol with misoprostol alone in management of EPF.Methods: This was a prospective comparative interventional randomised clinical study conducted at Shri Maharaja Gulab Singh hospital, Jammu, Jammu and Kashmir India from November 2019 to October 2020. A total of 200 patients with gestational age less than 13 weeks and ultrasound diagnosis of EPF were included in the study and randomly divided into two groups, group A (100 patients) received tab. mifepristone 200 mg orally 24 hrs before the use of Tab misoprostol 800 ug per vaginally. If no expulsion occurs within 4 hours, repeat doses of 400 ug misoprostol were given per vaginally at 4-hourly interval to a maximum of 2 doses in women less than or equal to 9 weeks by ultrasound and 4 doses in women more than 9 weeks by ultrasound. Group B (100 patients) received only Tab misoprostol in similar doses without prior mifepristone. The study was performed after approval from the institutional ethical committee. The data was analysed using computer software Microsoft Excel, Statistical and IBM SPSS version 21.0. The statistical difference in mean value between two groups was tested using unpaired ‘t’ test. The qualitative data was compared using Fischer’s exact test.Results: The success rate was higher in group A 92% than group B where it was 76%. The mean induction-abortion interval and dose of misoprostol required for expulsion were 6.56±.66 hrs in group A and 10.40±4.33 hrs in group B and 1126.88±536.06 ug in group A and 1583.33±364.58 ug in group B. The patients in group A experienced significantly less side effects than those in group B, 19% versus 32% and also required fewer blood transfusions than group B, 2% versus 5%.Conclusions: In the present study we came to the conclusion that mifepristone followed by misoprostol is more effective, safe and acceptable than misoprostol alone.

Comparison of efficacy of 600 and 800 micrograms vaginal misoprostol in early pregnancy failure in SMGS: a tertiary health care hospital in Jammu, India

Background: Misoprostol use in early pregnancy failure is varied and dose is not well established. Aim of this study was to compare efficacy and side effects of 600 versus 800 micrograms vaginal misoprostol in early pregnancy failure.Methods: A randomized prospective observational study was conducted in the postgraduate department of obstetrics and gynaecology, SMGS hospital Jammu from November 2018 to October 2019 after getting approval from the ethical committee. Hundred patients (50 in group A and 50 in group B) admitted in labour room before 12 weeks of gestation with an ultrasound diagnosis of early fetal demise (missed abortion or brightened ovum) were treated medically with different doses of vaginal misoprostol.Results: The success rate in patients in group A is 72% and group B is 88%, p=0.045 (difference is statistically significant). Patients who required suction and evacuation were 28% in group A and 12% in group B.Conclusions: Use of misoprostol for medical management of 1st trimester missed/anembryonic is an effective, cheap, safe and convenient alternative to surgical evacuation. It was concluded that 800 micrograms vaginal misoprostol is more effective than 600 micrograms vaginal misoprostol. But 800 micrograms misoprostol has more side effects than 600 micrograms vaginal misoprostol.

Q fever and early pregnancy failure: a Scottish case control study

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An Imbalance of IL-33/ST2-AXL-Efferocytosis Axis Induces Pregnancy Loss Through Metabolic Reprogramming of Decidual Macrophage

During the implantation of embryo, apoptosis is inevitable. These apoptotic cells (AC) are removed by efferocytosis, which fills the macrophage with a metabolite load nearly equal to the phagocyte itself. A timely question pertains to the interrelationship between efferocytosis metabolism and the immune behavior of decidual macrophages (dMΦs) and its effect on pregnancy outcome. Here we report a positive feedback of IL-33/ST2-AXL-efferocytosis leading to pregnancy failure through metabolic reprogramming of dMΦs. We compared the serum level of IL-33, sST2, along with IL-33, ST2, efferocytosis and metabolism of dMΦs from both normal gravidas and unexplained recurrent pregnancy loss (RPL) patients. And we revealed the disturbance of IL-33/ST2 axis, increased apoptotic cells and elevated efferocytosis of dMΦs from the patients with RPL. Afterwards the dMΦs swallowing so many apoptotic cells secreted more sST2 and less TGF-β, which polarized dMΦs towards M1 phenotype. Moreover, the elevated sST2 biased the efferocytosis metabolism of RPL dMΦs towards oxidative phosphorylation and exacerbated the disruption of IL-33/ST2 signaling pathway. The metabolic disorders also led to the dysfunction of efferocytosis, resulting in more uncleared apoptotic cells and the secondary necrosis occurred. We also screened efferocytotic molecule AXL regulated by IL-33/ST2. This positive feedback of IL-33/ST2-AXL-efferocytosis led to pregnancy failure. And the IL-33 knockout mice demonstrated poor pregnancy outcomes, and exogenous supplementation of mouse IL-33 could partially alleviate the fate of embryo losses. These findings highlight a new etiological mechanism whereby dMΦs leverage immunometabolism for the homeostasis of microenvironment at the maternal-fetal interface.

EFFICACY OF MIFEPRISTONE FOLLOWED BY MISOPROSTOL VERSUSMISOPROSTOL ALONE IN MEDICAL MANAGEMENT OF EARLY PREGNANCY FAILURE

Purpose of the study- To study the efcacy of mifepristone followed by misoprostol over misoprostol alone in early pregnancy failure in terms of complete evacuation of uterus. METHODS: In a randomized comparative study at the Department of Obstetrics and Gynaecology of Kasturba Hospital, 100 women with early pregnancy failure and gestational age ≤12 weeks between January 2017 and December 2017 were recruited. Of these, 50 women were given a single oral dose of mifepristone (200 mg) followed by 800 mcg misoprostol vaginally (if required) after 24 hours and the other 50 women were treated with 800 mcg misoprostol vaginally alone. RESULTS: Complete evacuation of uterus was achieved in 96% women treated with a sequential combination of mifepristone and misoprostol versus 84% women treated with misoprostol alone. The difference in the rate of complete expulsion was 12% (p <0.05, 95% CI). Also, pre-treatment with mifepristone resulted in statistically signicant reduction in induction to abortion interval (2.40 ± 1.774 vs 3.30 ± 1.951 hr), amount of bleeding (402.2 ± 111.84 vs 535.0 ± 114.84 ml) and duration of bleeding (10.7 ± 2.30 vs 12.4 ± 3.38 days). CONCLUSION Medical treatment of early pregnancy failure with a sequential combination of mifepristone and misoprostol was more effective than misoprostol alone. Hence, women with early pregnancy failure may be offered mifepristone pretreatment before misoprostol to increase the chance of successful management, while reducing the need for surgery.

Effect of Foot-and-Mouth Disease Vaccine on Pregnancy Failure in Beef Cows

This study evaluates whether the foot-and-mouth disease (FMD) vaccination increases pregnancy failures in Bos taurus beef cows. A total of 3,379 cows were assigned to two experimental groups to receive (n = 1,722) or not receive (n = 1,657) a FMD vaccine (commercial preparation containing FMD virus, O1 Campos and A24 Cruzeiro) at different gestational age. Pregnancy diagnosis was performed by ultrasonography at vaccination time (Day 0), and the cows were classified by days of pregnancy as follows: (a) &lt;29 days after mating (presumed pregnant cows, n = 778), (b) between 30 and 44 days of pregnancy (n = 1,100), (c) 45 and 59 days of pregnancy (n = 553), and (d) between 60 and 90 days of pregnancy (n = 948). Pregnancy failure was determined 30 days after vaccination by a second ultrasound examination. Cows that were vaccinated within 29 days after mating had a 7.8% greater pregnancy failure rate than non-vaccinated cows (44.1%, 163/370 vs. 36.3%, 148/408, respectively; P &lt;0.05). Cows vaccinated between 30 and 44 days of gestation had a pregnancy failure rate greater than non-vaccinated cows (4.9%, 28/576 vs. 2.5%, 13/524, respectively; P &lt;0.05). When cows received the vaccine between days 45 and 90 of gestation no differences in pregnancy failure were observed (0.8%, 6/776 vs. 1.2%, 9/725, respectively; P = NS). Body temperature and local adverse reactions to vaccine inoculation were recorded in a subset of 152 multiparous cows. Hyperthermia (&gt;39.5°C) was detected on Day 1 or 2 in 28.0% (21/75) of vaccinated vs. 7.8% (6/77) of non-vaccinated cows (P &lt;0.01). Local adverse reaction to the FMD vaccine inoculation increased from 0.0% (0/75) on Day 0, to 15.7% (11/75) on Day 4, and 38.7% (29/75) on Day 10 (P &lt;0.01). On Day 30 local reaction was detected in 10.5% (34/323) and fell to 2.2% on Day 60 (7/323) post vaccination (P &lt;0.01). In conclusion, FMD vaccine increases pregnancy failure when it is administered before 45 days of gestation, an effect that was associated with hyperthermia and local adverse reaction. No effect on pregnancy failure was found when vaccination was performed after 45 days of gestation.

Pathogenetic significance of the male factor in an uncompleted pregnancy

Introduction. When pregnancy failure occurs, not only the woman should be examined, but also her partner. Purpose of the study — to evaluate the significance of spermogram values in the partners of patients with an uncompleted pregnancy. Materials and methods. A retrospective comparative cohort study was conducted. A total of 197 married couples were ncluded in the study. Group 1 consisted of 71 couples with a history of miscarriag. Chromosomal abnormalities (CA) were detected during embryo cytogenetic examination in 45 cases; these patients were included in subgroup 1a; the rest constituted subgroup 1b. The control group (group 2) consisted of 126 couples without a history of pregnancy loss. A detailed anamnesis and general clinical examinations were performed in all the couples. Spouses of the patients underwent spermogram analysis. Results. The proportion of men who abused alcohol was higher in group 1 than in group 2 — 40.8% vs. 19% (p<0.01). In subgroup 1b chronic diseases were noted in 61.5% of men, in group 2 — only 28.6% (p<0.001). Differences in the number of men with normal spermogram were found between group 2 and subgroup 1b, 65.1% and 35.3%, respectively (p=0.036). In group 1, 45% of men had teratozospermia (43.5% in subgroup 1a, 47.1 in subgroup 1b) and in group 2, only 16.3% (p=0.004). Discussion. In most cases, the leading etiological factor in pregnancy failure is a chromosomal abnormality n the embryo (fetus). The role of the "male" factor is increasing in the genesis of pregnancy failure. Examination of thspouse should be an integral component of pre-conceptional preparation. Conclusion. Spousal alcohol abusrisk factor for CA in the embryo and for pregnancy failure. The presence of chronic diseases in the spouse is also a risk factor for pregnancy failure. Among the spermogram parameters, the number of spermatozoa with normal morphology is the most significant in assessing the ririsk of pregnancy failure in a married couple, teratozoospermia significantly increases the risk of non-pregnancy.

G-CSF: A Vehicle for Communication Between Trophoblasts and Macrophages, Which May Cause Problems in Recurrent Spontaneous Abortion

Background: The etiology of about half of patients with recurrent spontaneous abortion (RSA) remains unclear. Imbalance of the immune inflammatory response at the mother-foetal interface may be one of the keys to the onset of RSA. Granulocyte-colony stimulating factor (G-CSF) is thought to have a protective effect on pregnancy and its absence may lead to pregnancy failure. However, the evidence of the described effects of G-CSF is scant. This study aimed at investigating whether the loss of G-CSF induced RSA by affecting cell communication at the maternal-foetal interface.Results: It was found that G-CSF was mainly expressed in villus rather than decidua and expression in RSA tissues was lower than that in normal tissues. Further, the down-regulation of G-CSF in trophoblasts resulted to a decrease in cell activity. Trophoblast-derived exosomes inhibited macrophage activation, while G-CSF free exosomes did not. Intraperitoneal injection of G-CSF improved the pregnancy outcome in RSA mice and the expression of G-CSF as well as its receptor at the mother-foetal interface were also changed.Conclusion: The expression of G-CSF was found to be decreased in villi of patients with RSA. It was evident that the absence of G-CSF weakens the immune suppression of trophoblasts against macrophages and the function of trophoblasts is also impaired. Therefore, this may be a key factor in the occurrence of RSA. Further, G-CSF decreases the rate of abortion in RSA mice and may provide some assistance in the treatment of patients with RSA.

Menin directs regionalized decidual transformation through epigenetically setting PTX3 as an obstacle balancing FGF and BMP signaling

During programmed decidualization in rodents, uterine stromal cells undergo extensive cellular and molecular reprograming into morphologically and functionally distinct decidual cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. However, the underlying mechanism governing this spatiotemporal specificity of decidualization remains elusive. Here, we demonstrated that uterine deletion of Men1, a key component of the MLL1/2 histone methyltransferase complex, disrupted the terminal differentiation of stromal cells, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 distribution in chromatin recapitulates the enrichment of transcription active modification H3K4me3 orchestrating spatiotemporal decidualization of stromal cells. Further transcriptomic investigation demonstrates that Men1 directly regulated the expression of PTX3, an extra-cellular trap for FGF2, in a H3K4me3 dependent manner in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and stromal cell differentiation during decidualization. In brief, our study provides genetic evidence and molecular mechanism for epigenetic rewiring mediated decidual regionalization by Men1 and shed new light in pregnancy maintenance.