Recurrent Spontaneous Miscarriage Research Articles

Upregulation of GPR133 expression impaired the phagocytosis of macrophages in recurrent spontaneous miscarriage

ABSTRACT Decidual macrophages are the second-largest immune cell group at the maternal-foetal interface. They participate in apoptotic cell removal, and protect the foetus from microorganisms or pathogens. Dysfunction of decidual macrophages gives rise to pregnancy complications such as preeclampsia and recurrent spontaneous miscarriage (RSM). However, the mechanisms by which decidual macrophages are involved in the occurrence of adverse pregnancy outcomes have not been elucidated. Here we integrated DNA methylation and gene expression data from decidua macrophages to identify potential risk factors related to RSM. GPR133 was significantly hypomethylated and upregulated in decidual macrophages from RSM patients. Further demethylation analysis demonstrated that GPR133 expression in decidual macrophages was significantly increased by 5-Aza-dC treatment. In addition, the influence of GPR133 on the phagocytic ability of macrophages was explored. Phagocytosis was impaired in the decidual macrophages of RSM patients with increased GPR133 expression. Increased GPR133 expression induced by demethylation treatment in the decidual macrophages of healthy control patients led to a significant decrease in phagocytic function. Importantly, knockdown of GPR133 resulted in a significant improvement in the phagocytic function of THP-1 macrophages. In conclusion, the existing studies have shown the influence of GPR133 on the phagocytic function of decidual macrophages and pregnancy outcomes, providing new data and ideas for future research on the role of decidual macrophages in RSM.

Attenuated Total Reflectance–Fourier Transform Infrared (ATR-FTIR) Spectroscopy Combined With Deep Learning for Classification of Idiopathic Recurrent Spontaneous Miscarriage (IRSM)

Idiopathic recurrent spontaneous miscarriage (IRSM) is characterized by the repeated losses of two or more clinically detected pregnancies before 24 week of gestation with the cause remaining unknown. We aim to ascertain whether attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy with deep learning (DL) can accurately distinguish IRSM from controls. Endometrial tissue (internal lining of the uterine cavity) was collected from 20 women with IRSM and 20 controls during window of implantation. ATR-FTIR spectroscopy was used to acquire spectra (400–4000 cm−1) from three random locations across each specimen and averaged. Multivariate analysis was used to assess group differentiation. Furthermore, DL classifiers were implemented to predict IRSM. Hierarchical cluster analysis (HCA) demonstrated distinct clustering of the two groups. The principal component analysis (PCA) loading plot indicated contributions from amide I, II and III bands, symmetric methyl (CH3) bending of proteins, lipids, nucleic acids, asymmetric stretching of CH2 due to lipids, collagen, and glucose in discriminating between IRSM and controls. Supervised orthogonal projections to latent structures discriminant analysis (OPLS-DA) exhibited optimized discrimination between the groups. Convolutional neural network (CNN) and variational autoencoder-artificial neural network (VAE-ANN) classifiers exhibited good performance and showed classification accuracy of 94% and 94% and F1 scores (mean of recall and precision) of 95% and 93%, respectively. The optimal area under the receiver operating characteristic curve (AUC) value of both CNN and VAE-ANN was 0.94. ATR-FTIR spectroscopy combined with DL approach is promising for understanding complex disease pathophysiology and enabling early prediction.

CPY27B1-related vitamin D deficiency contributes to the impaired function of CD4+T cells in Recurrent spontaneous miscarriage

The study aimed to explore the relationship between the expression of cytochrome P450 family 27 subfamily B member 1 (CYP27B1), vitamin D, and impaired T cell subsets in recurrent spontaneous miscarriage (RSM). A Total of 779 healthy women of childbearing age and 1031 women with a history of RSM were involved in this study. The results of flow cytometry showed that the proportion of Tregs was higher in healthy women than in the women with RSM. For cytokines, the levels of interleukin-17 (IL-17) and interferon-gamma (IFN-γ) were significantly higher in RSM patients than in healthy women, while IL-10 was notably lower in RSM patients. Furthermore, compared to healthy individuals, RSM patients had lower levels of serum 25(OH)D detected by chemiluminescence. The frequency of Tregs was negatively correlated with 25(OH)D. Specifically, for every 10 ng/ml increase in 25(OH)D, the percentage of Tregs increased by 0.58 as calculated. IL-17 and IFN-γ were inversely correlated with 25(OH)D, while the serum interleukin-10 (IL-10) level was positively correlated with 25(OH)D. CYP27B1 was found to be expressed in both cytotrophoblast and extracellular villi trophoblast cells. However, reduced expression of CYP27B1 was observed in the placenta with RSM. Notably, the level of 25(OH)D increased in the supernatant of CYP27B1 knockdown BeWo compared to normal cells, while human chorionic gonadotropin (hCG) was significantly reduced. The hCG secretion of CYP27B1 KO BeWo cells was partially restored after 1,25(OH)2D3 supplementation. In addition, 1,25(OH)2D3 treatment could induce more CD4+ T cells to convert to Foxp3+iTreg, which in turn inhibited the secretion of IL-17, IFN-γ. In summary, this research unveiled a connection between reduced CYP27B1 and vitamin D deficiency in RSM. Our study underscores the potential benefits of vitamin D treatment supplementation in the context of RSM. However, it is important to note that further research is imperative to validate these observations.

Platelet Glycoprotein Receptor Ia-C807T and IIIa-PlA1/PlA2 Genetic Polymorphisms Are Associated With Enhanced Platelet Function in Women With Recurrent Miscarriages.

Thrombophilic genetic polymorphisms of the platelet glycoproteins Ia (GpIa) and IIIa (GpIIIa) have been associated with an increased risk of recurrent miscarriages. The aim of this study was to investigate the association of genetic polymorphisms GpIa-C807T and GpIIIa-T1565C-PlA1/PlA2 with platelet function in women with unexplained spontaneous recurrent miscarriages. This cross-sectional study comprised 196 unrelated nulliparous Greek women with a history of unexplained recurrent miscarriages. Patients were genotyped for the presence of the GpIa-C807T (rs1126643) and GpIIIa-T1565C-PlA1/PlA2 (rs5918) genetic polymorphisms by pyrosequencing, and the collagen/epinephrine closure time (COL/EPI CT) of the subjects was assessed using the platelet function analyzer (PFA)-100. In the total population of women with recurrent miscarriages, the COL/EPI CT ranged from 70 to 160 seconds (median: 122 seconds, interquartile range (IQR): 102.3-138 seconds). In comparison with the double homozygotes CC/PlA1PlA1 that had the most prolonged CT (mean: 131.9 ± 17.5 seconds), the COL/EPI CT was statistically significantly shorter for the GpIa-807T single carriers (mean: 120.3 ± 20.9 seconds) (p=0.011) (absolute difference: 11.6 seconds, 95% confidence interval (CI): 21.2 to -2.0 seconds;relative difference: -9%, 95% CI: -16% to -2%), and the GpIIIa-PlA2 single carriers also displayed a trend for shorter COL/EPI CT (mean:121.3 ± 23.7 seconds) (p=0.141) (absolute difference: -10.6 seconds, relative difference: -8%), whereas the combined carriers of the GpIa-807T and the GpIIIa-PlA2 alleles exhibited the shortest COL/EPI CT (mean: 104.1 ± 19.7 seconds) (absolute difference: -27.7 seconds, 95% CI: -39.1 to -16.3 seconds; relative difference: -21%, 95% CI: -30% to -12%) (p<0.001). In comparing genotype frequencies in the lower half with those in the upper half of the COL/EPI CT range, the GpIa-807T and the GpIIIa-PlA2 single carriers were associated with higher odds of COL/EPI CT < 122 seconds (odds ratio (OR)=3.4, 95% CI: 1.5 to 7.5, p=0.002, and OR=2.6, 95% CI: 1.0 to 7.2, p=0.053, respectively). The association was strongest for the combined carriers with OR of 15.0 (95% CI: 5.2 to 43.2, p<0.001) for COL/EPI CT below the medianand OR of 35.5 (95% CI: 4.4 to 284.5, p<0.001) for COL/EPI CT < 100 seconds. The GpIa-C807T and GpIIIa-PlA1/PlA2 polymorphisms and more pronouncedly the combined carriers of the risk variants are associated with enhanced platelet reactivity expressed via shorter COL/EPI CT. These findings provide further evidence for the role of platelet-associated genetic thrombophilia in the pathogenesis of recurrent miscarriages and promotethe analysis of platelet function as a diagnostic tool in the evaluation of this disorder.

Prevalence and pregnancy outcome in antiphospholipid syndrome: an observational study

Antiphospholipid syndrome (APS) is an autoimmune disorder characterized by vascular thrombosis, both arterial and venous, and recurrent spontaneous pregnancy loss due to circulating antiphospholipid antibodies (aPL) including anticardiolipin antibodies (aCL) and/or anti-glycoprotein I antibodies (anti-GPI). This observational study was conducted among antenatal women at OBG Department, IMS, and SUM Hospital, Bhubaneswar, over a year from March 2020 to 2021. Of 1260 cases, 25 were diagnosed with ALPA syndrome, with a prevalence rate of 1.98%. The most common age was 26-30 years (40%) with a mean age of 28.83 ± 3.26 years. The primary cause was recurrent 1st-trimester spontaneous miscarriage. Beta 2 glycoprotein antibody was most prevalent (40%). Significant associations were found in hypertensive and FGR APLA patients compared to non-hypertensive and non-FGR APLA patients. Hypertension and FGR occurred in 24% and 20% of APLA patients, respectively. Preterm delivery rate was higher (52%) in APLA syndrome, without significant association. B2GP antibody was linked to the lowest live birth rate, and highest rates of preeclampsia, IUGR, and stillbirth. Screening for B2GP antibodies is recommended for FGR and early onset preeclampsia cases with/without previous spontaneous pregnancy loss.

The Main Causes of Recurrent Spontaneous Miscarriages

Summary: Repeated spontaneous miscarriages are defined as at least three consecutive episodes of spontaneous miscarriage, less than 14 weeks of amenorrhea, with the same partner, in a patient under 40 years of age. 80% of these patients have an identifiable cause justifying an etiological approach. A guided history and clinical examination are necessary. An etiological assessment is to be carried out: a pelvic ultrasound and a hormonal assessment in the woman, as well as a karyotype of the two members of the couple. The other examinations are requested as a second intention. The main causes are balanced chromosomal abnormalities of the parents, sperm DNA fragmentation, congenital malformations and lesions of the uterine cavity, anti-phospholipid syndrome, unbalanced diabetes, dysthyroidism and luteal insufficiency. In the event of an identified cause, certain therapeutic or preventive measures must be discussed in order to limit the risk of recurrence.

Dysregulated Gln-Glu-α-ketoglutarate axis impairs maternal decidualization and increases the risk of recurrent spontaneous miscarriage

Recurrent spontaneous miscarriage (RSM) affects 1%-2% of fertile women worldwide and poses a risk of future pregnancy complications. Increasing evidence has indicated that defective endometrial stromal decidualization is a potential cause of RSM. Here, we perform liquid chromatography with mass spectrometry (LC-MS)-based metabolite profiling in human endometrial stromal cells (ESCs) and differentiated ESCs (DESCs) and find that accumulated α-ketoglutarate (αKG) derived from activated glutaminolysis contributes to maternal decidualization. Contrarily, ESCs obtained from patients with RSM show glutaminolysis blockade and aberrant decidualization. We further find that enhanced Gln-Glu-αKG flux decreases histone methylation and supports ATP production during decidualization. Invivo, feeding mice a Glu-free diet leads to a reduction of αKG, impaired decidualization, and an increase of fetal loss rate. Isotopic tracing approaches demonstrate Gln-dependent oxidative metabolism as a prevalent direction during decidualization. Our results demonstrate an essential prerequisite of Gln-Glu-αKG flux to regulate maternal decidualization, suggesting αKG supplementation as a putative strategy to rectify deficient decidualization in patients with RSM.

Quantitative analyses of cytokine profiles reveal hormone-mediated modulation of cytokine profiles in recurrent spontaneous miscarriage

PurposeCytokines play important roles in pregnancy complications. Some hormones such as estrogen, progesterone, and dydrogesterone have been shown to alter cytokine profiles. Understanding how cytokine profiles are affected by these hormones is therefore an important step towards immunomodulatory therapies for pregnancy complications. We analyse previously published data on the effects of estrogen, progesterone, and dydrogesterone on cytokine balances in women having recurrent spontaneous miscarriages. Materials and methodsLevels of eight cytokines (IFN-γ, IL-2, IL-6, IL-10, IL-13, IL-17, IL-23, TNF-α) from n = 22 women presenting unexplained recurrent spontaneous miscarriages were studied. Cytokine values were recorded after in vitro exposure of peripheral blood cells to estrogen, progesterone, and dydrogesterone. We expand on earlier analysis of the dataset by employing different statistical techniques including effect sizes for individual cytokine values, a more powerful statistical test, and adjusting p-values for multiple comparisons. We employ multivariate analysis methods, including to determine the relative magnitude of the effects of the hormone therapies on cytokines. A new statistical method is introduced based on pairwise distances able to accommodate complex relations in cytokine profiles. ResultsWe report several statistically significant differences in individual cytokine values between the control group and each hormone treated group, with estrogen affecting the fewest cytokines, and progesterone and dydrogesterone both affecting seven out of eight cytokines. Exposure to estrogen produces no large effects sizes however, while IFN-γ and IL-17 show large effect sizes for both progesterone and dydrogesterone, among other cytokines. Our new method for identifying which collections (i.e. subsets) of cytokines best distinguish contrasting groups identifies IFN-γ, IL-10 and IL-23 as especially noteworthy for both progesterone and dydrogesterone treatments. ConclusionsWhile some statistically significant differences in cytokine levels after exposure to estrogen are found, these have small effect sizes and are unlikely to be clinically relevant. Progesterone and dydrogesterone both induce statistically significant and large effect-size differences in cytokine levels, hence therapy with these two progestogens is more likely to be clinically relevant. Univariate and multivariate methods for identifying cytokine importances provide insight into which groups of cytokines are most affected and in what ways by therapies.

Genetic Evaluation of Spontaneous Miscarriages and Couples through Conventional and Modern Diagnostic Tools

Background: Genetic causes of miscarriages have been extensively reported and studied in almost half of the first-trimester pregnancy losses, for the reason genetic investigations of the products of conceptions (POCs) are crucial to help identify possible genetic etiology. This information is helpful for the devastated parents as it provides them with more acceptance of the loss and helps them recognize possible recurrence risks. Objective: This study aims to evaluate QF-PCR for chromosomal aneuploidies detection and to explore potential parental chromosomal abnormalities causing recurrent spontaneous miscarriages. Methodology: A total of seventy-six products of conceptions (POCs) were obtained from the Gynecology department of Civil Hospital, Karachi. Further blood samples from forty-five couples were also collected in addition to ninety-three maternal blood samples. All of these samples were subjected to amplify short tandem repeat (STR) for common chromosomal aneuploidies (13, 18, and 21). Real-time QF-PCR was performed on 76 POCs on Sansure Biotech Inc, Changsha, China, using primers D13S631 and D13S634 for chromosome 13, D18S386 and D18S535 for chromosome 18, and D21S1411 and D21S1414 for chromosome 21. Parental blood samples were examined by both QF-PCR and karyotyping for cross-checking with their POC. Chromosome 16 was used as an internal control for the amplification of each reaction. Statistical analysis was done by using SPSS version 24. Results: QF-PCR analysis revealed chromosomal aneuploidies among twenty-nine POCs with the highest number of trisomy 13 followed by trisomy 21 and then trisomy 18 while all the parental samples were normal. Nine cases of chromosomal abnormalities were ruled out through karyotyping from parental blood samples further, a Robertsonian translocation was observed through conventional cytogenetics and interestingly the corresponding POC was found to have trisomy 21. Conclusion: This study’s findings endorsed QF-PCR as an efficient technique to detect chromosomal aneuploidies. As QF-PCR was found to be less laborious, has lesser turnaround time, is more economical, and has a low failure rate than karyotyping.

CD4+ and CD8+ preimplantation endometrial population in women with unexplained recurrent miscarriage.

The aim of this study is to assess the secretory-phase endometrial leucocytes in women with 2 or more unexplained abortions and in healthy controls. This cross-sectional study was performed in 3 tertiary centres: Ain Shams University, Al-Azhar, and October 6 University Maternity Hospitals. The study included 50 women who consented to participate in this study. Women were divided in 2 groups; the first group consisted of 25 non-pregnant women with unexplained recurrent pregnancy loss, while the second group (n = 25) included non-pregnant women as a control group who had no history of recurrent pregnancy loss. Endometrial biopsies were taken from all participants around the expected time of implantation (one week after induction of ovulation by human chorionic gonadotrophins) to elucidate the T lymphocyte population, CD4+ (helper-T) and CD8+ (suppressor-T) markers. Women with 2 or more unexplained abortions had significantly less endometrial CD8+ (p < 0.05), and consequently their endometrial CD4/CD8 ratio was higher in relation to the controls. There was no significant difference in endometrial CD4+ in relation to controls (p > 0.05). From the results we can conclude that CD8 is more valuable than CD4 in women with recurrent spontaneous miscarriage. CD8 is better positive than negative in such patients.

A retrospective study of pregnancy outcomes when intravenous immunoglobulin is used for the treatment of recurrent spontaneous miscarriages with subchorionic hematoma

Objective: To investigate the incidence of subchorionic hematoma (SCH), pregnancy outcomes and health status of offspring in patients with recurrent spontaneous miscarriage (RSA) treated with intravenous immunoglobulin (IVIg). Methods: The records of 775 patients with RSA were retrospectively reviewed. RSA with SCH were all treated with IVIg. Pregnancy outcomes examined were the rates of miscarriage, stillbirth, pre-term birth, and live birth. The pregnancy complications and comorbidities examined included oligohydramnios, hypertensive disorders, gestational diabetes, premature membrane rupture, placental adhesions, placenta previa, postpartum hemorrhage, placental abruption, and low birth weight. The health status of offspring of RSA patients with SCH was followed up by telephone, record physical and neurodevelopmental performance, and diseases under 5 years old, then compare with common children. Based on the ratio of SCH volume to that of the gestational sac, SCH was divided into small (ratio &lt; 20%), moderate (ratio = 20%–50%), and large (ratio &gt; 50%). Statistical analysis was performed with IBM SPSS Statistics 23.0. Comparison of continuous variables was analyzed using t-test. Categorical variables were compared by using χ2 test or Fisher’s exact test. Multivariable logistic regression was used for adjusting certain confounders. Results: Of the 775 patients with RSA, 110 RSA had a SCH (incidence = 14.2%). SCH was firstly found at 8.29 (5.00–11.58) weeks pregnant. There was no statistical difference in age, number of pregnancies, parity and miscarriages between patients with and without an SCH. The incidence of SCH in in-vitro fertilization embryo transfer (IVF-ET) patients was higher than in natural pregnancy patients (27.9% vs. 13.1%, P &lt; 0.05). RSA with SCH patients with pregnancy outcome data called Group A (n = 94), RSA without SCH patients with pregnancy outcome data called Group B (n = 556), the rates of miscarriage (17.0% vs.12.4%), stillbirth (0 vs. 0.4%), pre-term delivery (9.6% vs. 10.8%), live birth (84.7% vs. 80.9%), and pregnancy complications were not different between Group A and B. The rate of vaginal bleeding in the Group A was higher than in the Group B (P &lt; 0.05). There was no significant difference in the birth weight, the rate of low birth weight infants, neonatal asphyxia, or neonatal pneumonia between the groups. 43 puerpera in the experimental group were willing to receive telephone follow-up, who gave birth from December 2015 to November 2016. A total of 43 live births were delivered. By March 2022, the children were 5 years and 4 months old to 6 years and 3 months old. There is no difference in the physical development compared with common children. A child was diagnosed with neuropsychological delay. The incidence rate of community acquired pneumonia (CAP) was 27.9 per 1000 person-years for children under 5 years. In patients with a SCH and vaginal bleeding, the rate of preterm birth was 16.7%. The rate of preterm birth was highest (36.4%) in RSA patients with a large SCH, and only 5.7% in patients with a small SCH (P &lt; 0.05). Patients treated with IVIg had mild adverse reactions such as hypothermia, dizziness, and rash with rates of 1.8%, 1.8%, and 0.9%, respectively. Conclusion: The incidence of SCH was 14.2% in RSA. Pregnancy outcomes were similar between the RSA patients with a SCH treated with IVIg treatment and RSA patients without a SCH. There is no difference in the physical development between offspring of RSA with SCH and common children, and effect of SCH on neurodevelopment of offspring needs to be further verified by expanding the sample size. RSA patient with a SCH are prone to have vaginal bleeding and abdominal pain. For RSA patients with a SCH and vaginal bleeding, or SCH volume ratio &gt; 50%, even after IVIg, still leads to a significantly higher preterm birth rate.

Evaluation of homocysteine, folic acid and methylenetetrahydrofolate reductase C677T gene polymorphism associated with recurrent spontaneous miscarriage

This study was aimed to assess the association between evaluation of homocysteine level, folic acid and methylenetetrahydrofolate reductase MTHFR C677T gene polymorphism and recurrent pregnancy loss RSA. Sixty four women diagnosed with RSA and 41 normal fertile female, who had at least one or more child, 21 of them were pregnant women while 20 were non-pregnant. The level of homocysteine was high in women with RSA (11.41+3.75) (p&lt;0.05) compared to normal fertile women either pregnant (7.02+2.13) or non-pregnant (6.84+2.08), low levels of folic acid was observed (6.35+2.09) in women with RSA (p&lt;0.05) compared to fertile women either pregnant(10.08+3.08) or non-pregnant(11.27+3.15). No statistically significant difference was observed in the distribution of genotypes between cases and controls for MTHFR polymorphism. In conclusion, the present study reveals to lack of association of MTHFR C677T polymorphism in RSA women.

Role of Yoga Prana Vidya (YPV) System Protocols in Infertility Treatment: A Case Study of A 29-Year-Old House Wife with History of Recurrent Spontaneous Miscarriages and Ovarian Cysts

INTRODUCTION: Recurrent spontaneous miscarriage (RSM) affects 1 to 2 % of women causing anxiety and worry for self and family. Ovarian cysts are perhaps the most common issue among women trying to conceive. This paper presents a case of a 29-year-old married woman having ovarian cyst and suffered two miscarriages, was treated successfully using YPV healing protocols. METHOD: This paper used case study method going through patient medical records, healer’s records and patient feedback. RESULTS: The patient experienced successful pregnancy and delivered a healthy baby boy after a C-section procedure. There were no health issues of baby and the mother post-delivery. A follow up after 9 months confirmed that the mother and her baby both were in good health. CONCLUSIONS: YPV system protocols have been established as complementary as well as alternative medicine to treat and cure a variety of health conditions. Further research is recommended. It will be worthwhile to consider imparting a working knowledge of YPV system protocols to frontline healthcare workers including doctors and nurses to enable them to render holistic treatment in a safe process at low cost CONCLUSIONS: YPV system protocols have been established as complementary as well as alternative medicine to treat and cure a variety of health conditions. Further research is recommended. It will be worthwhile to consider imparting a working knowledge of YPV system protocols to frontline healthcare workers including doctors and nurses to enable them to render holistic treatment in a safe process at low cost

Role of Yoga Prana Vidya (YPV) System Protocols in Infertility Treatment: A Case Study of A 29-Year-Old House Wife with History of Recurrent Spontaneous Miscarriages and Ovarian Cysts

Role of Yoga Prana Vidya (YPV) System Protocols in Infertility Treatment: A Case Study of A 29-Year-Old House Wife with History of Recurrent Spontaneous Miscarriages and Ovarian Cysts

P-577 A Therapeutic Protocol in Previous Failed ART Patients With High Total NK Cells: An RCT

Abstract Study question To evaluate a combined therapeutic protocol of lipid emulsion, prednisolone &amp; LMWH in cases of failed ART cycles with high NK cells Summary answer The combined therapy of lipid emulsion, prednisolone &amp; LMWH had a higher pregnancy rate but not significant than the standard therapy alone. What is known already Many researchers have proved that a high numbers and/or cytotoxicity of peripheral blood NK cells is associated with infertility, recurrent spontaneous miscarriage (RSM) and failed ART cycles. Many investigations have shown that intralipid has the ability to suppress NK cell activity. It is well known that parenteral fat emulsions accumulate in macrophages modifying many immune responses. So, modifying the T helper1/ T helper 2 balance in favor of T helper 2 with implantation chances increase. Prednisolone has an immunosuppressive and anti-inflammatory actions and has widely used in autoimmune diseases. Prednisolone also reduces the high numbers of uNK in RSM. Study design, size, duration This was a prospective randomized controlled trial in 100 cases with failed ART cycles &amp; high NK cells. From Jan 2019- Dec 2021 Participants/materials, setting, methods One hundred failed ART cases with high NK cells were divided into 2 groups: (Control group)(50 cases) with previous failed ART cycles will undergo standard treatment (progesterone, low dose aspirin &amp; folic a.). While the other (Interventional group)(50 cases) will have in addition to the previous protocol: lipid emulsion begin in the cycle before embryo transfer &amp; prednisolone begin with the start of lipid emulsion &amp; LMWH begin with the day of ET Main results and the role of chance Chemical pregnancy was higher in the interventional group (54.0%) than the control group (40.0%) but without statistical significance (P = 0.161). Also, ongoing pregnancy was higher in the interventional group (85.0%) than the control group (60.0%) but without statistical significance (P = 0.094). No significant difference was reported regarding clinical pregnancy (P = 0.943). Limitations, reasons for caution Wider implications of the findings Our results suggest a hopeful therapeutic protocol that may be used in such failed ART cases especially when no other reason can be found. But selecting which cases will benefit the most will need much further investigations. Trial registration number NCT03792997

Cytokines and pregnancy complications: modulation for prevention and treatment

“There is many a slip twist the cup and the lip” is a proverb that dates back to the 3rd century. This proverb comes to mind while writing a review on pregnancy loss; so many complications can occur between fertilization and development of the embryo through the long period of gestation until successful delivery of the baby. These include failure of implantation of the embryo, spontaneous miscarriage in the first trimester, pre-eclampsia in the second trimester, premature rupture of fetal membranes, pre-term labour, and pre-term delivery. The maternal immune system which does a phenomenal job of protecting the host from a daunting variety of infections, sometimes also mounts adverse reactions that complicate pregnancy and endanger the fetus. Maternal immune reactions that can adversely affect pregnancy have been shown to be mediated by lymphocytes, macrophages and natural killer cells, and by cytokines secreted by these cellular effectors. This review summarizes the deleterious effects of cytokines leading to recurrent spontaneous miscarriage, pre-eclampsia and pre-term delivery, which are the major complications of pregnancy. It then goes on to discuss the potential use of progesterone and dydrogesterone, an orally-administered progestogen, as immunomodulatory molecules that can be considered for the prevention and/or treatment of these complications.

Association of Polymorphisms in miR146a, an Inflammation-Associated MicroRNA, with the Risk of Idiopathic Recurrent Spontaneous Miscarriage: A Case-Control Study.

It has been established that microRNAs (miRNAs) are involved in the regulation of immune responses and serve as biomarkers of inflammatory diseases as well as recurrent spontaneous miscarriage (RSM). Herein, we aimed to study the relationship between three functional miR146a gene polymorphisms with idiopathic RSM (IRSM) susceptibility. We recruited 161 patients with IRSM and 177 healthy women with at least one live birth and without a history of abortion. Genotyping was performed using RFLP-PCR and ARMS-PCR methods. We found that the rs6864584 T/C decreased the risk of IRSM under dominant TT+TC vs. CC (OR = 0.029) and allelic C vs. T (OR = 0.028) contrast models. Regarding rs2961920 A/C and rs57095329 A/G polymorphisms, the enhanced risk of IRSM was observed under different genetic contrasted models, including the codominant CC vs. AA (OR = 2.81 for rs2961920) and codominant GG vs. AA (OR = 2.36 for rs57095329). After applying a Bonferroni correction, haplotype analysis revealed a 51% decreased risk of IRSM regarding the ACA genotype combination. This is the first study reporting that miR146a rs57095329 A/G, rs2961920A/C, and rs6864584 T/C polymorphisms are associated with the risk of IRSM in a southern Iranian population. Performing replicated case-control studies on other ethnicities is warranted to outline the precise effects of the studied variants on the risk of gestational trophoblastic disorders.

OBSTETRICAL PROGNOSIS AFTER UTERINE SEPTUM SECTION BY HYSTEROSCOPYABOUT A CASE REPORT

The septate uterus is the most common congenital uterine malformation resulting from a resorption defect of the inter-mullerian septum. It is frequently associated with conception abnormalities such as early recurrent spontaneous miscarriage (FCS) and late recurrent miscarriage (FCT) but also with fertility abnormalities, without a clear mechanism. The imaging techniques used to diagnose a septate uterus are based on : Endo-vaginal ultrasound, diagnostic hysteroscopy and IRM pelvic . Surgical treatment is based on septum sectioning which is a minimally invasive surgical technique with low risk of complications. This septal section significantly improves the obstetrical prognosis in women with a desire for pregnancy.

Appraisals of Sero-detection of Treponema pallidum Antibodies IgG and IgM and CBC parameters among Spontaneous Recurrent Miscarriage in Women- Case-Control Study in Gezira State 2018

Objectives: We determined Sero-detection of Treponema pallidum (IgG and IgM antibodies) using ELIZA techniques women with recurrent Miscarriage in Gezira state and appraisal of other risk factors.&#x0D; Methods: in this case-control, a hospital-based study conducted at Wad Madani teaching hospital Department of Obstetrics gynecological, Gezira State, Sudan. Ninety subjects were involved, 45 were women with recurrent Miscarriage, and controls were healthy pregnant women (no miscarriage). Serum Treponema pallidum antibodies were estimated by the ELIZA method.&#x0D; Results: Sero-detection of IgG and IgM antibodies by using ELIZA techniques, a total of 45 miscarriage women (cases) for IgM 6 (13.3%) were positive, and 39 (48.8%) were negative for Treponema pallidum by using ELISA techniques. A total of 45 non-miscarriage women (control) for IgM 4 (8.9%) were positive, and 41(91.1%) were negative For Treponema pallidum by using ELISA techniques. A total of 45 miscarriage women (cases) for IgG 13(28.9%) were positive, 32(71.1%) were negative. Furthermore, IgG for non-miscarriage, like IgM 4(8.9%), was positive, and 41(91.1%) were negative.&#x0D; Conclusion: Higher prevalence of Treponema pallidum IgG seropositivity among pregnant women who reported miscarriages compared to those who did not report miscarriages (p &lt; 0.001) while no association between IgM seropositivity and pregnant women who reported miscarriages.

MiR-187 regulates the proliferation, migration and invasion of human trophoblast cells by repressing BCL6-mediated activation of PI3K/AKT signaling.

Recurrent miscarriage (RM), refers to two or more consecutive spontaneous miscarriage in a pregnant woman. RM is caused by many factors, and microRNAs play an important role in the development and pathology of RM. In the present study, we investigated the function of miR-187 in the pathogenesis of RM and its effects on human trophoblast cells. The localization of miR-187 in the human placenta in early pregnancy was determined by in situ hybridization. QRT-PCR was used to detect the expression of miR-187 in villi of normal early pregnancy induced abortion group and recurrent spontaneous miscarriage group. Then, HTR8/SVneo cells were used to investigated the effect of miR-187 on BCL6 expression and biological activity of trophoblasts. We found that the expression of miR-187 in villi of RM group was higher than that of normal abortion group and miR-187 inhibited the proliferation, migration, and invasion of HTR8 cells. We also found that miR-187 promoted apoptosis, inhibited EMT, and inhibited the PI3K/AKT pathway in HTR8 cells. In addition, we also found that BCL6 is a direct target of miR-187 and is negatively regulated by miR-187. In addition, BCL6 reversed the inhibitory effects of miR-187 on HTR8/SVneo cells. These data demonstrate that miR-187-induced repression of PI3K/AKT signaling is mediated by BCL6 in HTR8 cells. MiR-187 inhibits the proliferation, migration, and invasion of trophoblasts through a mechanism that involves regulation of BCL6.