scholarly journals Extracellular Vesicles: An Important Biomarker in Recurrent Pregnancy Loss?

2021 ◽  
Vol 10 (12) ◽  
pp. 2549
Author(s):  
Nina Rajaratnam ◽  
Nadja E. Ditlevsen ◽  
Jenni K. Sloth ◽  
Rikke Bæk ◽  
Malene M. Jørgensen ◽  
...  

Recurrent pregnancy loss (RPL) has an estimated incidence of 1–3% of all couples. The etiology is considered to be multifactorial. Extracellular vesicles (EVs) take part in numerous different physiological processes and their contents show the originating cell and pathophysiological states in different diseases. In pregnancy disorders, changes can be seen in the composition, bioactivity and concentration of placental and non-placental EVs. RPL patients have an increased risk of pregnancy complications. The aim of this prospective study was to examine whether measuring different specific EV markers in plasma before and during pregnancy could be used as predictors of pregnancy loss (PL) in women with RPL. Thirty-one RPL patients were included in this study; 25 had a live birth (LB group) and six had a new PL (PL group). Five blood samples were obtained, one before achieved pregnancy and the others in gestational week 6, 8, 10 and 16. Moreover, some of the patients received intravenous immunoglobulin (IVIG) infusions as part of treatment, and it was also examined whether this treatment influenced the EV levels. Seventeen EV markers specific for the immune system, coagulation, placenta and hypoxia were analyzed in the samples with EV Array, a method able to capture small EVs by using an antibody panel targeting membrane proteins. Comparing the LB and PL groups, one EV marker, CD9, showed a significant increase from before pregnancy to gestational week 6 in the PL group. The changes in the other 16 markers were nonsignificant. One case of late-onset PL showed steeply increasing levels, with sudden decrease after gestational week 10 in nine of 17 markers. Moreover, there was an overall increase of all 17 markers after IVIG treatment in the LB group, which was significant in 15 of the markers. Whether increases in EVs positive for CD9 characterize RPL patients who subsequently miscarry should be investigated in future larger studies.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ka Ying Bonnie Ng ◽  
George Cherian ◽  
Alexandra J. Kermack ◽  
Sarah Bailey ◽  
Nick Macklon ◽  
...  

AbstractIt is known that lifestyle factors affect sporadic miscarriage, but the extent of this on RPL (recurrent pregnancy loss) is less well known. A systematic review and meta-analysis was performed to assess the associations between lifestyle factors and RPL. Studies that analysed RPL in the context of BMI, smoking, alcohol and caffeine intake were included. The primary and secondary outcomes were odds of having RPL in the general population and odds of further miscarriage, respectively. Underweight and women with BMI > 25 are at higher odds of RPL in the general population (OR 1.2, 95% CI 1.12–1.28 and OR 1.21, 95% CI 1.06–1.38, respectively). In women with RPL, having BMI > 30 and BMI > 25 has increased odds of further miscarriages (OR 1.77, 95% CI 1.25–2.50 and OR 1.35, 95% CI 1.07–1.72, respectively). The quality of the evidence for our findings was low or very low. Being underweight and BMI > 25 contributes significantly to increased risk of RPL (general population). BMI > 25 or BMI > 30 increases the risk of further miscarriages (RPL population). Larger studies addressing the effects of alcohol, cigarette smoking and caffeine on the risk of RPL with optimisation of BMI in this cohort of women are now needed.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Sofoklis Stavros ◽  
Despoina Mavrogianni ◽  
Myrto Papamentzelopoulou ◽  
Evaggelos Basamakis ◽  
Hend Khudeir ◽  
...  

Abstract Background Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, −238G > A, −308G > A and − 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women. Methods This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples. Results The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births. Conclusions This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, −238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.


2021 ◽  
Vol 10 (2) ◽  
pp. 179
Author(s):  
Emma Rasmark Roepke ◽  
Ole Bjarne Christiansen ◽  
Karin Källén ◽  
Stefan R. Hansson

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.


Author(s):  
Tamilmani Subi ◽  
Vinodhini Krishnakumar ◽  
Chandreswara Raju Kataru ◽  
Inusha Panigrahi ◽  
Meganathan Kannan

Many studies have reported the association of VEGF-1154G/A, VEGF 936C/T and p53 Arg72Pro polymorphisms with Recurrent Pregnancy Loss (RPL), but the outcomes are inconsistent. We have used meta-analysis to associate these polymorphisms with RPL, having the spiral artery remodelling as a major risk factor. The studies were identified from three different reputed databases, namely Science direct, PubMed/Medline and Scopus. The eligible studies of VEGF-1154G/A, VEGF 936C/T and p53Arg72Pro polymorphisms associated with the RPL were selected for the analysis. They were segregated into three different ethnic groups as Asians, Caucasians and mixed population. For the analysis, the overall prevalence, Odds ratio, Risk ratio, Relative risk ratio and P values were calculated. A total of 3241 RPL cases and 3205 healthy controls from 21 different case-control studies were analysed. RPL was highly prevalent in mixed population with VEGF-1154G/A and p53 Arg72Pro polymorphisms (70.04% and 66.46% respectively) and in Asian population with VEGF 936C/T polymorphism (53.58%). The homozygous recessive genotypes of VEGF and p53 exhibited significant association between the respective polymorphisms and RPL along with the increased risk of outcome. The current analysis conclusively reports the geographic distribution of the different genetic polymorphisms which shows high association with the progression of RPL. Understanding the spectrum of polymorphisms on different population with the spiral artery remodelling as a risk factor encloses the importance of the vasculature during the pregnancy.


2018 ◽  
Vol 6 (4) ◽  
pp. 98 ◽  
Author(s):  
Fatemeh Karami ◽  
Maliheh Askari ◽  
Mohammad Modarressi

Thrombophilia gene variants have been shown to be associated with higher risk of recurrent pregnancy loss (RPL). Due to the role of human platelets antigen 1 (HPA-1) and fibrinogen β chain (FGB) as critical players in the coagulation process, their most important variants including rs5918 T > C and rs1800790 G > A were selected to be studied in women affected by RPL. Three milliliters of peripheral blood were drawn from 110 women with history of at least two consecutive spontaneous abortion and 110 healthy women controls. rs5918 T > C and rs1800790 G > A of HPA-1 and FGB genes, respectively, were selected to be analyzed through polymerase chain reaction-restriction fragment length polymorphism (PCR_RFLP) following DNA isolation using QIAamp DNA Blood Mini Kit. Heterozygote genotype (TC) of HPA-1 gene rs5918 polymorphism was significantly associated with risk of RPL (p-value = 0.02). Although, rs1800790 G > A of FGB gene was not associated with RPL, its combination with rs5918 polymorphism was associated with increased risk of RPL. Owing to the critical roles of FGB and HPA-1 genes in coagulation, and thrombosis and several confinements on the meaningful association between the combination of those polymorphism with risk of RPL, including them in the thrombophilia panel may increase detection rate of hereditary thrombophilia patients. However, further studies with larger sample sizes are required to shed light on the exact role of the studied gene polymorphism, especially rs1800790 G > A of FGB gene variant in pathogenesis of RPL.


2018 ◽  
Vol 241 ◽  
pp. 969-977 ◽  
Author(s):  
Kai-Wei Liao ◽  
Pao-Lin Kuo ◽  
Han-Bin Huang ◽  
Jung-Wei Chang ◽  
Hung-Che Chiang ◽  
...  

2020 ◽  
Vol 9 (9) ◽  
pp. 2833 ◽  
Author(s):  
Carlo Ticconi ◽  
Adalgisa Pietropolli ◽  
Monia Specchia ◽  
Elena Nicastri ◽  
Carlo Chiaramonte ◽  
...  

The aim of this prospective cohort study was to determine whether women with recurrent pregnancy loss (RPL) have an increased risk of pregnancy complications compared to normal pregnant women. A total of 1092 singleton pregnancies were followed, 431 in women with RPL and 661 in normal healthy women. The prevalence of the following complications was observed: threatened miscarriage, miscarriage, cervical insufficiency, chromosomal/genetic abnormalities, fetal anomalies, oligohydramnios, polyhydramnios, fetal growth restriction, intrauterine fetal death, gestational diabetes mellitus (GDM), preeclampsia, placenta previa, abruptio placentae, pregnancy-related liver disorders, and preterm premature rupture of the membranes. The odds ratio and 95% CI for each pregnancy complication considered were determined by comparing women with RPL and normal healthy women. Women with RPL had an overall rate of pregnancy complications higher than normal women (OR = 4.37; 95% CI: 3.353–5.714; p < 0.0001). Their risk was increased for nearly all the conditions considered. They also had an increased risk of multiple concomitant pregnancy complications (OR = 4.64; 95% CI: 3.10–6.94, p < 0.0001). Considering only women with RPL, women with ≥3 losses had a higher risk of pregnancy complications than women with two losses (OR = 1.269; 95% CI: 1.112–2.386, p < 0.02). No differences were found in the overall risk of pregnancy complications according to the type, explained or unexplained, of RPL. Women with secondary RPL had an increased risk of GDM than women with primary RPL. Pregnancy in women with RPL should be considered at high risk.


2017 ◽  
Vol 79 (2) ◽  
pp. e12799 ◽  
Author(s):  
Yael Lichtman ◽  
Eyal Sheiner ◽  
Tamar Wainstock ◽  
Idit Segal ◽  
Daniella Landau ◽  
...  

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