PLT antigen discrepancy pattern among couples with recurrent abortion.

Background: Recurrent abortion refers to a condition of two or more consecutive pregnancies without known etiology affected by miscarriage before the completion of the 20th week of gestational age. However, several hypotheses have been proposed, but not much data are available concerning the relationship between human platelet antigens (HPAs) polymorphisms and recurrent abortion. This study was conducted to evaluate the genetic differences between HPA-1, -2, -3, -5, and - 15 in Iranian couples with a history of recurrent abortion. Methods: In this cross-sectional study, a total of 74 couples with at least 2 recurrent abortions without any known specified reasons enrolled in the study. HPA polymorphisms genotyping was performed by single-specific primer PCR. Genotype frequency was calculated using the Hardy-Weinberg equation. Results: A total of 39 couples (52.7%) had HPA genotyping partial mismatches. The most common partial mismatch pairs were found concomitantly on both HPA-15a and HPA-15b in three couples (4%), followed by two (2.7%) on HPA-3a and one (1.3%) in each HPA-2b and HPA-5b. There was a deviation from the Hardy-Weinberg equilibrium in the HPA-2 and -5 systems. Conclusion: The present study declared that partial mismatches of HPA-3 and -15 genotypes were common among Iranian couples due to the history of recurrent abortion and approximately half of the couples carried at least one HPA gene that was absent in their partners. Further studies might be helpful to clarify the association between HPA polymorphisms and recurrent abortion, such as an investigation into the alloantibodies against HPAs.

Cytogenetics investigation in 151 Brazilian infertile male patients and genomic analysis in selected cases: experience of 14 years in a public genetic service.

OBJECTIVES: Male infertility accounts for approximately 30% of cases of reproductive failure. The characterization of genetic variants using cytogenomic techniques is essential for the adequate clinical management of these patients. We aimed to conduct a cytogenetic investigation of numerical and structural rearrangements and a genomic study of Y chromosome microdeletions/microduplications in infertile men derived from a single centre with over 14 years of experience. RESULTS: We evaluated 151 infertile men in a transversal study using peripheral blood karyotypes and 15 patients with normal karyotypes through genomic investigation by multiplex ligation-dependent probe amplification (MLPA) or polymerase chain reaction of sequence-tagged sites (PCR-STS) techniques. Out of the 151 patients evaluated by karyotype, 13 presented chromosomal abnormalities: two had numerical alterations, and 11 had structural chromosomal rearrangements. PCR-STS detected a BPY2 gene region and RBMY2DP pseudogene region microdeletion in one patient. MLPA analysis allowed the identification of one patient with CDY2B_1 and CDY2B_2 probe duplications (CDY2B and NLGN4Y genes) and one patient with BPY2_1, BPY2_2, and BPY2_4 probe duplications (PRY and RBMY1J genes).

Treatment with plasma exchange of a pregnant woman with anti-PP1Pk alloimmunization: A case report.

The histo-blood group antigens P, P1 and Pk are a closely related set of glycosphingolipid structures expressed by red blood cells and other tissues. None of these three characters is expressed on p cells, a null phenotype that arises in the context of homozygous mutation of the A4GALT gene. Subjects with p phenotype spontaneously develop a natural alloantibody named anti-PP1Pk, which is a mixture of IgG and IgM against P1, P and Pk. While anti-P1 is a weak cold antibody with poor clinical significance, anti-P and anti-Pk antibodies are potent haemolysins responsible for severe hemolytic transfusion reactions. The rare anti-PP1Pk alloantibodies are associated with recurrent spontaneous abortion in the first trimester of gestation. P and Pk antigens are expressed at high levels on the placenta and antibodies directed against both these structures are deleterious to placental trophoblasts. Here we describe the use of plasma exchange (PEX) in a nulliparous 39-year-old woman with anti-PP1Pk antibodies and a history of repeated spontaneous early abortions and hypofertility. The patient underwent apheresis starting from the third week throughout the pregnancy and a healthy child was delivered by cesarean section at 35 WG. The newborn required only phototherapy within a few days of life. We can state that an early treatment with the only PEX has proven to be effective and safe in the management of a fetomaternal P-incompatibility caused by a high anti-PP1Pk titer (256).

Study the effect of recombinant leukemia inhibitory factor on maintenance of pregnancy and frequency of regulatory T cells in abortion-prone mice.

Recurrent spontaneous abortion (RSA) can have a significant impact on a woman's quality of life. Understanding the mechanisms behind abortion is crucial for developing potential treatments. Among various models of abortion, the CBA/J(♀) × DBA/2J(♂) model stands out as the most extensively studied. This model reveals the influence of an altered immune system on resorption during pregnancy. The leukemia inhibitory factor (LIF) holds considerable importance as a secretory glycoprotein essential for successful implantation. Regulatory T cells (Tregs) have been found to produce high levels of LIF in both mice and humans. LIF plays a vital role in the development of Tregs by upregulating the expression of the Foxp3 transcription factor while downregulating the expression of RORγt. To investigate the impact of recombinant LIF (rLIF) on pregnancy maintenance and Treg cell frequency in abortion-prone (AP) mice, a specific recombinant protein was used in this study. The AP group consisted of CBA/J(♀) × DBA/2J(♂) mice, while the control group comprised CBA/J(♀) × BALB/c(♂) mice. Intraperitoneal injections of rLIF were administered to the AP group on the third day of pregnancy, and its effects on Treg cell frequency and pregnancy maintenance were examined during this period. Following rLIF injections on the fourteenth day of pregnancy, the expression of Foxp3 significantly increased in AP mice (p = 0.02,0.008). Additionally, AP mice injected with rLIF demonstrated a significant reduction in resorption rate (p = 0.01) and a notable increase in birth rate (p = 0.01,0.0005). These findings provide new insights into the potential benefits of LIF in treating RSA patients.

Determination of chlamydial load in recurrent miscarriage in relation to some female sex hormones: a case-control study.

INTRODUCTION: Chlamydia trachomatis is a frequent cause of adverse pregnancy outcomes including recurrent spontaneous abortion (RSA). However, regulation of infectious load by host immune response is unknown. Female sex hormones are known to affect C. trachomatis infection. The aim of this study was to determine correlation of chlamydial infectious load and gestational age with concentration of progesterone/estrogen in RSA. METHODOLOGY: Urine and non-heparinized blood were collected from patients with history of > 3 spontaneous abortions (n = 150, cases) and those with history of > 2 successful deliveries (n = 150, controls) from Department of Obstetrics and Gynecology, Safdarjung hospital, New Delhi, India. C. trachomatis positivity was determined by polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA) and chlamydial load by real-time PCR. Estrogen and progesterone concentrations were estimated by ELISA and correlated with chlamydial load. RESULTS: 22/150 case patients were positive for C. trachomatis. 2,000-10,000 copies/mL of chlamydial load were detected in infected RSA patients. Progesterone concentration showed significant decrease while estrogen concentration was significantly increased in C. trachomatis-positive RSA patients versus controls. Chlamydial load and estrogen concentration were positively correlated while progesterone concentration was negatively correlated with chlamydial load. Gestational age was positively correlated with concentration of estrogen and negatively correlated with concentration of progesterone in infected-RSA women. CONCLUSIONS: Overall findings suggest that interplay between chlamydial copy load, hormonal changes such as increased expression of estrogen and decreased expression of progesterone, and advanced gestational age may be contributing as deciding factors for ensuing RSA during C. trachomatis-infection.

Cellular Functions of High-Temperature Requirement Factor A4 in Placenta.

The expression of High-temperature requirement factor A4 (HtrA4) mRNA is significantly lower in the chorionic villi of patients with recurrent pregnancy loss (RPL) than in the control group. We conducted an investigation into the cellular functions of HtrA4 using the CRISPR/Cas9 system and shRNA-HtrA4 to create knockout BeWo cells and HtrA4 knockdown JEG3 cells. Our results indicated that the knockout BeWo cells exhibited reduced capacity for invasion and fusion, but increased levels of proliferation and migration, with a significantly shortened cell cycle compared to wild-type cells. Wild-type BeWo cells highly expressed cell invasion- and fusion-related factors, while knockout BeWo cells highly expressed migration-, proliferation-, and cell cycle-related factors. The shRNA-HtrA4 JEG3 cells showed a decreased capacity for invasion, but an increased capacity for migration, accompanied by a decrease in the expression of cell invasion-related factors and an increase in migration-related factors. Moreover, our ELISA results revealed that the serum HtrA4 level was lower in patients with RPL than in the controls. These findings suggest that HtrA4 depletion may be associated with placental dysfunction.

Hyperhomocysteinemia and pregnancy outcomes in women with polycystic ovary syndrome: A case-control study.

Background: One of the reproductive medicine challenges is to determine the role of hyperhomocysteinemia in the pathogenesis of polycystic ovary syndrome (PCOS), especially in women with recurrent pregnancy loss (RPL). Objective: Determine the correlation between hyperhomocysteinemia and pregnancy outcome in women with PCOS. Materials and Methods: This case-control study involved 245 women (20-30 yr) and was conducted in Georgia, Tbilisi from 2019-2022. Of these, 175 were women with PCOS (study group) and 70 were healthy women (control group). Women with PCOS were divided into group I with RPL (n = 90), and group II with live births (n = 85). Group I was divided into subgroups A and B with and without insulin resistance. The investigation measured homocysteine (Hcy), follicle-stimulating, luteinizing, anti-Mullerian hormones, total and free testosterone were determined. To determine the ovarian volume and antral follicle count, participants also underwent an ultrasound examination. Results: In women with PCOS, the average Hcy level was significantly higher than in the controls, p < 0.05. In group I, the average Hcy level was significantly higher than in group II and controls, p < 0.05. There was no significant difference in average Hcy level between group II and controls. The average Hcy level in group I, subgroup A was significantly higher than in subgroup B, p < 0.05. The average total, free testosterone levels, and homeostatic model assessment-insulin resistance levels (HOMA-IR) in group I was significantly higher than in group II and controls. HOMA-IR in group II and controls did not differ significantly. The average anti-Mullerian hormone levels in women with PCOS were significantly higher than controls, p < 0.05. No significant difference was observed in average anti-Mullerian hormone level, ovarian volume, antral follicle count, and body mass index between the comparison groups of PCOS. In group I, a positive correlation between Hcy with HOMA-IR was detected. Conclusion: Serum Hcy levels are elevated in women with PCOS and RPL, which correlates with their insulin resistance status.

Possible Role of Leukemia Inhibitory Factor and Inflammatory Cytokines in The Recurrent Spontaneous Abortion: A Case-Control Study.

BACKGROUND: Despite of long-lasting efforts, in more than 50% of cases, the etiology of recurrent spontaneous abortion (RSA) remains unknown. Leukemia inhibitory factor (LIF) has an essential role in the reproductive process, such as modulating inflammatory responses. This study aimed to evaluate the relationship between the LIF gene expression as well as serum levels of inflammatory cytokines and occurrence of RSA in infertile women with a history of RSA. MATERIALS AND METHODS: In this case-control study, the relative gene expression levels of LIF, concentrations of tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-17 were measured in peripheral blood and serum of women with a history of RSA (N=40) compared with non-pregnant and fertile women as the control group (N=40) using quantitative real-time polymerase chain reaction and the enzyme-linked immunosorbent assay, respectively. RESULTS: The mean age of patients and controls was 30.1 ± 4.28 and 30.03 ± 4.23, respectively. Patients had a history of at least 2 and at most 6 abortions. The mRNA levels of LIF were significantly lower in the women with RSA in comparison with the healthy participant (P=0.003). Regarding cytokine levels, no significant difference was seen between the two groups (P≥0.05). There was no correlation - between the LIF mRNA levels and TNF-α and IL-17 serum concentrations. The U-Mann-Whitney test and the Pearson correlation coefficient were applied to comparison variables between groups as well as a correlation between LIF mRNA and cytokine levels in serum. CONCLUSION: Despite a significant reduction in the LIF gene mRNA level in patients with RSA, it was not associated with increases in inflammatory cytokines. Dysfunction in the production of LIF protein may be involved in the onset of RSA disorder.

Clinical observation of Gushen antai pill combined with heparin sodium in the treatment of anticardiolipin antibody-positive recurrent abortion / 中国药房

OBJECTIVE To investigate the clinical efficacy of Gushen antai pills combined with heparin sodium in the treatment of antiphospholipin antibody （ACA）-positive recurrent abortion. METHODS A total of 203 ACA-positive recurrent abortion patients were randomly divided into control group （n＝101） and combination treatment group （n＝102）. Control group was additionally treated with heparin sodium on basis of basic treatment， and combination treatment group was additionally treated with Gushen antai pills on the basis of control group. Serum samples were collected from patients， the levels of interleukin 6 （IL- 6）， tumor necrosis factor α （TNF-α）， cyclooxygenase 2 （COX-2）， β-human chorionic gonadotropin （β-HCG） and ACA were detected by enzyme-linked immunosorbent assay. The antibody-negative conversion rate was calculated， the clinical efficacy of the patient was observed， and the occurrence of adverse drug reactions was recorded. RESULTS After treatment， the pregnancy success rate and antibody-negative conversion rate of combination treatment group were significantly higher than those in the control group （P＜0.05）， and the abortion rate was significantly lower than that in the control group （P＜0.05）. Compared with before treatment， serum levels of IL-6， TNF-α and ACA in 2 groups were decreased significantly （P＜0.05）， while the levels of COX-2 and β-HCG were increased significantly （P＜0.05）； the changes of above indexes in combination treatment group were more significant（P＜0.05）. There was no statistical significance in the incidence of adverse drug reactions between 2 groups（P＞0.05）. CONCLUSIONS Gushen antai pills can maintain high expression of β-HCG， reduce the level of ACA and improve immune microenvironment in patients with ACA-positive recurrent abortion by increasing the serum level of COX-2 and decreasing the serum level of IL-6， so as to increase the success rate of pregnancy.

Expression and mechanism of micro-ribonucleic acid-29a in chorionic villi obtained at curettage with recurrent abortion.

Objective: Explored the expression of miR-29a in puerpera with RSA and its influencing mechanism. Method: 52 patients with RSA group were divided into 30 cases representing ≤3 abortions and 22 cases with ≥4 abortions,thirty healthy women who had induced abortion during the same period as the control group. The differences in the expression levels of miR-29a, FKBP52 mRNA, VEGF, MVD, and HIF-lα were compared between the groups by conducting a correlation analysis. Results: The expression levels of miR-29a, VEGF, MVD, and HIF-lα in the chorionic villus were significantly higher among patients in the group with ≥4 abortions than in those in the group with ≤3 abortions (P < 0.05), and the expression levels of FKBP52 mRNA were lower in the former than in the latter (P < 0.05). A Spearman correlation analysis revealed that the expression levels of miR-29a were positively correlated with the levels of VEGF, MVD, and HIF-lα (P < 0.05) and negatively correlated with the expression level of FKBP52 mRNA (P < 0.05). Conclusion: MiR-29a may be involved in the pathogenesis of RSA by inhibiting the protein expressions of FKBP52 and VEGF, promoting the apoptosis of trophoblasts, and impairing neovascularization, resulting in placental vascular dysplasia..

The association of IL-3, IL-17A, and IL 27 serum levels with susceptibility to toxoplasmosis in recurrent abortion of Iraqi women.

Cytokines are a group of immunomodulatory proteins leading to a variety of immune reactions in the human; these cytokines play a significant role in the development of appropriate immune responses against T. gondii. This study aims to reveal the association of toxoplasmosis with serum levels of IL-3, IL-17A, and IL-27 in aborted women. The blood samples of patients and controls were collected from Al-Alawiya Maternity Teaching Hospital/Baghdad/Iraq from 2019 to 2020 for detecting anti-T. gondii antibodies (IgG and IgM) and the level of interleukins by ELISA. The results of TORCH by rapid test for recurrent abortion recorded 25.3% seropositive for anti-Toxoplasma antibodies, and 31.5% seropositive for one or more cases of TORCH test (Cytomegalovirus, Rubella, and Herpes). Whereas the results for anti-T. gondii IgG and IgM antibodies were shown elevated positivity percentages by ELISA test; these percentages were 56.2% in recurrent abortion women with significant differences (P < 0.05). The results suggested that the IL-3 serum concentration of pregnant women, recurrent abortion, and recurrent abortion with toxoplasmosis was declined versus healthy women with significant differences (p < 0.05). However, the results revealed that the concentration of IL-17A in recurrent abortion, and recurrent abortion with toxoplasmosis elevated versus healthy women and pregnant women with significant difference (p < 0.05). Whereas the results indicated that the IL-27 serum concentration elevated with significant differences in recurrent abortion with toxoplasmosis group compared to healthy women, pregnant women, and recurrent abortion. Interestingly, the serum levels for IL-27 increased comparing to the levels of IL-3 and IL-17A in all groups with significant differences (P < 0.05). In conclusion, it appeared in this study that the role of IL-3, IL-17A, and IL-27 in the maternal immune response during infections can lead to abortion.

The effect of hydroxychloroquine on pregnancy outcomes in patients with unexplained recurrent pregnancy loss: a placebo-controlled study "pilot study".

This double-blind placebo-controlled study investigated the effect of hydroxychloroquine on pregnancy outcomes in people with unexplained recurrent pregnancy loss (URPL). The inclusion criteria included gestational age ≤6 weeks and a history of at least two miscarriages. The exclusion criteria included any known cause for previous abortions or a history of any chronic diseases. Participants were given 200 mg hydroxychloroquine or placebo twice a day until gestational week 20. Twenty-nine women were enrolled. There was no statistically significant difference between the two groups in terms of age, BMI, gravidity, previous abortion, relative married couple, and infertility. Miscarriage occurred in five women including one in the hydroxychloroquine group (7.69%) and four women in the placebo group (28.57%) (OR: 2.36, 95% PL CI:1.07, 8.93). However, after adjusting for potential confounders, there was no significant difference between the two groups (aOR: 2.96, 95%CI: 0.91, 10.02).IMPACT STATEMENTWhat is already known on this subject? Miscarriage, a prevalent concern in the field reproductive medicine, causes psychological and family problems for couples. Unfortunately, no effective treatment has been yet found for URPL. There are some hypotheses about the role of immunological factors in URPL. Hydroxychloroquine (HCQ) has various immunological effects and may theoretically have a role in the treatment of URPL. Although few studies have been registered to investigate the effect of HCQ on URPL, none of them has been published.What do the results of this study add? In our double-blind placebo-controlled trial, the prevalence of abortion in the HCQ group was four times lower than that in the placebo group, however, this difference was not statistically significant, which can be attributed to the small sample size.What are the implications of these findings for clinical practice and/or further research? We hope that HCQ will be of interest to researchers and future research help clarify the role of HCQ in preventing URPL.

The association between serum level and genetic variation of IL-3 (rs40401) in recurrent abortion women infected with toxoplasmosis in Iraq.

Toxoplasmosis is one of the most infections during pregnancy transmitted from mother to child via the placenta and causes morbidity and mortality prenatally. IL-3 is a hematopoiesis enhancing factor and assist in the implantation embryo and placental growth. The objective of this study is to provide valuable information about the risks of IL-3 elevated levels in aborted women with toxoplasmosis by determining the risk, or the protective role of alleles or genotypes for single nucleotide polymorphism (SNP) of IL-3 (rs40401) which might have a relationship with the susceptibility to toxoplasmosis. The levels of IL-3 in blood samples of patients and controls were detected by ELISA while the allelic discrimination method was used for SNP IL-3 (rs40401). The results suggested the IL-3 serum concentration of healthy pregnant women(HP), recurrent abortion women without toxoplasmosis (RAWOT), and recurrent abortion women with toxoplasmosis(RAWT) was declined versus healthy non pregnant women (HNP) with a statistically significant difference (p < 0.05). Moreover, the results SNP of IL-3 showed no significant association between patients and controls. Considering the distribution of serum levels for IL-3 by SNPs, the results have shown the serum level of IL-3 for the genotype CC, CT, TT in RAWOT and RAWT declined comparing to HNP women with significant differences (p < 0.05). In conclusion, SNP of IL-3 has not represented as a risk factor in recurrent abortion women with toxoplasmosis. Although the serum levels of IL-3 differed in patients according to genotype with significant differences compared to control.

Cyclosporine A to Treat Unexplained Recurrent Spontaneous Abortions: A Prospective, Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial.

BACKGROUND: The World Health Organization (WHO) has defined Unexplained Recurrent Spontaneous Abortion (URSA) as three and more consecutive miscarriages before the 20th week of gestation. To date, empiric therapy for patients with unexplained recurrent pregnancy loss (URPL) is not precise. Studies have shown that URSAs are associated with Th1/Th2 and Th17/Treg immune imbalances at the maternal-fetal interface. The immunosuppressant cyclosporine A (CsA) is widely used in patients with organ transplantation or autoimmune diseases, and it has a good safety profile in pregnant women. However, high-quality evidence for CsA treatment of URSAs is lacking. Our purpose with this study is to evaluate the efficacy and safety of CsA for improving pregnancy outcomes in patients with URSAs and to explore the role of CsA in regulating the immune balance. METHODS/DESIGN: We expect to officially initiate our study at the Taizhou People's Hospital in March 2022. We defined the live birth rate as the primary outcome, and the secondary outcomes include the rates of successful pregnancy, miscarriage, pregnancy complications, and adverse pregnancy outcomes, and newborn birth weights. Patients who meet URSA eligibility criteria will be randomized in a 1:1 ratio into either a study group receiving CsA 2 weeks after fertilization or a control group receiving placebo at 2 weeks after fertilization (the women in both groups will receive the relevant treatment for 6 months). In addition, we will collect peripheral blood samples of the participants before and after the treatments, and we will isolate mononuclear cells and measure cytokine levels (IFN-γ, TNF-α, IL-2, IL-10, IL-6, IL-4) and Th1/Th2, Th17/Treg ratios. DISCUSSION: This is the first randomized controlled trial to evaluate the clinical and immunomodulatory effects of CsA on the pregnancy outcomes of women with URSA and our results will provide evidence to evaluate the use of CsA as a treatment for women with URSAs.

Identification of Balanced and Unbalanced Complex Chromosomal Rearrangement Involving Chromosomes 1, 11, and 15.

Chromosomal abnormalities are the common genetic factors that significantly impact fertility, miscarriage possibility and abnormal offspring with unbalanced karyotype. Complex chromosomal rearrangements (CCRs) refer to structural rearrangements which involve more than two breakpoints and often more than two chromosomes. According to the mode of transmission, they can be either familial or de novo rearrangements. Here we report a complex chromosomal rearrangement leading to intellectual disability, speech delay and multiple dysmorphic features, including cleft lip and inguinal hernia. Proband karyotype shows 46,XY,ins (1::11) (q42→qter::q25) compatible to partial trisomy 1 q42→qter, while the karyotype of his mother was 45,XX, ins (1::15) (q42;q11.1→qter), t (1;11)(q42,q25) compatible to apparently normal female phenotype.

Non-Coding RNAs Regulate Placental Trophoblast Function and Participate in Recurrent Abortion.

Recurrent spontaneous abortion (RSA) is a serious pregnancy complication with an increasing clinical incidence. The various causes of recurrent abortion are complicated. Developments in genetics, immunology, and cell biology have identified important roles of non-coding RNAs (ncRNAs) in the occurrence and progress of recurrent abortion. NcRNAs can affect the growth, migration, and invasion of placental trophoblasts by regulating cell processes such as the cell cycle, apoptosis, and epithelial-mesenchymal transformation. Therefore, their abnormal expression might lead to the occurrence and development of RSA. NcRNAs include small nuclear RNA (snRNA), small nucleolar RNA (snoRNA), ribosomal RNA (rRNA), transfer, RNA (tRNA), circular RNA (cRNA), and Piwi-interacting RNA (piRNA). In this review, we discuss recent research that focused on the function and mechanism of microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNA (circRNA) in regulating placental trophoblasts. The use of ncRNAs as potential diagnostic and predictive biomarkers in RSA is also discussed to provide future research insights.

Effectiveness of the use of Low Molecular Heparin in patients with repetition abortion history: Systematic review and meta-analysis.

OBJECTIVE: To evaluate the efficacy and safety of using low molecular weight heparin (LMWH) in women with a history of recurrent abortion without an identified cause. METHODS: To develop a systematic review to select the studies. Total found 437 papers. Seven studies were completed or requested. The following variables were analyzed: clinical pregnancy, implantation rate, live births, abortion, premature birth, pregnancy, continuous pregnancy, beyond the 20th gestational week, congenital abnormality, hemorrhage, preeclampsia, placental premature detachment. RESULTS: The LMWH group had a higher incidence of continuous pregnancy after the 20th week of gestation and there was no significant difference between the LMWH group and the expectant management group in the analysis of other variables. CONCLUSIONS: There was no data showing risk and/or less use of LMWH compared to expectant management; on the contrary, LMWH use increased the incidence of evolutionary pregnancy after the 20th gestational week. LMWH has some influence on prophylactic treatment of repeat abortion for unknown cause.

The efficacy of enoxaparin for recurrent abortion: a meta-analysis of randomized controlled studies.

Introduction: The efficacy of enoxaparin for recurrent abortion remains controversial. We conduct a systematic review and meta-analysis to explore the influence of enoxaparin versus placebo on recurrent abortion.Methods: We search PubMed, Embase, Web of Science, EBSCO, and Cochrane Library databases through February 2019 for randomized controlled trials (RCTs) assessing the effect of enoxaparin versus placebo on recurrent abortion. This meta-analysis is performed using the fixed or random-effect model when appropriate.Results: Six RCTs involving 1034 patients are included in the meta-analysis. Overall, compared with control group for patients with recurrent abortion, enoxaparin has no obvious impact on live births (RR = 1.06; 95% CI = 0.97-1.16; p = .17), abortion rate (RR = 0.71; 95% CI = 0.45-1.10; p = .13), birth weight (std. MD = 0.38; 95% CI = -0.21-0.96; p = .21), preterm delivery (RR = 0.55; 95% CI = 0.30-1.00; p = .05), preeclampsia (RR = 1.52; 95% CI = 0.42-5.51; p = .52), and postpartum hemorrhage (RR = 1.17; 95% CI = 0.69-1.99; p = .55).Conclusions: Enoxaparin may provide no significant benefits to patients with recurrent abortion.

Are alterations in melatonin and inflammatory cytokine serum levels linked with recurrent abortion in pregnant women with acute toxoplasmosis: The interacted nexus.

OBJECTIVE: To investigate melatonin serum level and inflammatory biomarkers in acute toxoplasmosis in pregnant women with recurrent abortions. METHODS: The case-control study was conducted at the Department of Parasitology, together with the Department of Obstetrics, Al-Yarmouk teaching hospital, Baghdad Iraq, from September 2018 until February 2019. Included were 60 pregnant women in first trimester with acute toxoplasmosis (n=28) or without toxoplasmosis (n=32) and with the history of recurrent abortions with a control group of healthy pregnant women (n=25). Melatonin and interleukins (IL-10, 1L-12) serum levels were evaluated in all groups. The data analysis was done by using SPSS 20. RESULTS: The mean serum melatonin level was lower in the pregnant women with acute toxoplasmosis (69.57±17.37 pg/ml) as compared to the pregnant women without acute toxoplasmosis (77.25±24.35 pg/ml), but the difference was not significant (p=0.43). Healthy pregnant women had a higher serum melatonin level (117.48±34.88 pg/ml) compared with the pregnant women with/without acute toxoplasmosis and a history of recurrent abortions. IL-10 serum level was higher in the healthy controls (12.73±2.58 pg/ml) as compared with the pregnant women with acute toxoplasmosis (5.50±1.92pg/ml) or without acute toxoplasmosis (8.50±2.53 pg/ml), (p<0.0001). Serum melatonin level was positively correlated with serum IL-10 level (P<0.001, r=0.94), and negatively correlated with serum IL-12 level in pregnant women with recurrent abortions with or without acute toxoplasmosis. CONCLUSIONS: Acute toxoplasmosis during pregnancy increases the risk of abortion through reduction of maternal serum melatonin level and dysregulation of pro-inflammatory/inflammatory cytokines axis.

Does LIN28B gene dysregulation make women more likely to abort?

BACKGROUND: LIN28B plays an important role in early embryonic development, but its role in villous trophoblast implantation and differentiation remains unknown. This study aims to verify the role of LIN28B in trophoblastic villous tissue and cells from women with URSA (unexplained recurrent spontaneous abortion) and artificial termination of pregnancy (negative control, NC). METHODS: The LIN28B gene and its protein expression level were detected with real-time quantitative PCR, Western immunoblotting analysis, and immunocytochemistry. The gene was also overexpressed in chorionic villous cell lines (HTR-8/SVneo and BeWo) to examine its effect on trophoblast function. RESULTS: The expression of LIN28B mRNA and protein of URSA villi was lower than that in the NC group. At the cellular level, overexpression of LIN28B enhanced cellular migration, and invasion, and inhibited apoptosis. LIN28B may inhibit apoptosis by promoting Akt phosphorylation and by inhibiting Bad phosphorylation and Bcl-2 expression. In addition, LIN28B inhibited cell fusion and reduced cellular syncytia. CONCLUSIONS: LIN28B can inhibit cell invasion and migration in vitro and promote apoptosis and fusion. The low expression of LIN28B in URSA villous trophoblast cells may be one of the causes of abortion. The role of LIN28B in villous trophoblasts needs further study. LAY SUMMARY: Propagation of offspring is of great significance to the continuation of the human race. However, continuous pregnancy is more difficult for some women, especially women who have multiple miscarriages. One important contributor is the cessation of development caused by genetic factors of the embryo, but there are still many unknown reasons. We investigated the LIN28B gene which is a possible pathogenic factor in the placenta. We collected 25 cases of abortion in the experimental group (unexplained recurrent abortion group) and 25 in the control group (artificial termination of pregnancy group): on average at 7-8 weeks of pregnancy. We tested the function of lin28b in these samples and verified its function in cell lines. LIN28B plays an important role in maintaining early pregnancy by promoting the invasion of villous cells, inhibiting apoptosis and fusion, and the reduction of LIN28B expression may lead to the occurrence of early miscarriage.