History Of Unexplained Recurrent Pregnancy Loss Research Articles

Treating unexplained recurrent pregnancy loss based on lessons learned from obstetric antiphospholipid syndrome and inherited thrombophilia: A propensity-score adjusted retrospective study

The efficacy of low molecular weight heparin (LMWH) is well-established in patients with obstetric antiphospholipid syndrome (O-APS). Their role in women with unexplained recurrent pregnancy loss (U-RPL) and late obstetrical complications (intrauterine growth restriction, IUGR and preeclampsia) is controversial. Here we compared rates of miscarriage and late obstetrical complications in RPL patients diagnosed with O-APS (n = 57) or hereditary thrombophilia (n = 25) (both assuming LMWH from the beginning of pregnancy) and in patients with a history of U-RPL (n = 118), assuming or not LMWH, followed at the ‘Pregnancy at risk’ and ‘Recurrent pregnancy loss’ outpatient clinics at the San Raffaele Hospital from April 2010 to April 2020. Patients with systemic autoimmune diseases other than primary O-APS were excluded. We tested for bivariate or multivariate associations among adverse pregnancy outcomes, the presence of thrombophilia and LMWH use by using chi-square test, Anova, propensity score adjusted univariate logistic regression and multivariate analysis as appropriate. U-RPL patients assuming LMWH from the beginning of pregnancy (group A) had a significantly lower rate of miscarriage compared to U-RPL patients who were not treated with LMWH (group B) (13 % vs. 41 % respectively, p 0.001) and similar pregnancy rates compared to both O-APS patients with a history of RPL taking LMWH (group C, 18 %) and RPL patients with thrombophilia and treated with LMWH (group D, 16 %). Our data highlight a protective effect of LMWH on miscarriage in patients with a history of U-RPL. In these patients, LMWH seems as effective as in O-APS and hereditary thrombophilia in reducing RPL

Evaluation of the Effects of 1,25 Vitamin D3 on Regulatory T Cells and T Helper 17 Cells in Vitamin D-deficient Women with Unexplained Recurrent Pregnancy Loss

Vitamin D insufficiency and deficiency can be associated with adverse effects on pregnancy outcomes, which may include recurrent pregnancy loss through the mechanisms that are yet unknown. The aim of this study was to evaluate the effect of 1,25VitD3 on regulatory T cells (Tregs) and T helper17 (Th17) cell populations In vitro in unexplained recurrent pregnancy loss (URPL) patients and healthy women. Samples from 20 non-pregnant women with a history of URPL were compared to 20 normal non-pregnant women. Peripheral blood mononuclear cells (PBMC) were divided into 3 wells for each subject: in the presence of 1, 25 VitD3 (50 nM, for 16 hours), PHA (positive control) (10μM), and without any treatment (as a baseline or negative control). The percentage of regulatory T cells and Th17 cells was measured by flow cytometry at baseline and then after cell culture experiments. Our study indicated that the percentage of Tregs in patients with URPL was significantly lower than the control group (2.42 ± 0.27 vs. 3.41 ± 0.29, P= 0.01). The percentage of Th17 cells was significantly greater in URPL patients compared to the control group (2.91 ± 0.33 vs. 1.18± 0.15, P=0.001). 1, 25VitD3 treatment significantly increased the percentage of Tregs from the baseline in the URPL group compared to that in the control group (1.23 ± 0.03 vs. 1.00 ± 0.03, P= 0.01). Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests supplementation of women with Vit D pre-pregnancy may be protective against URPL.

Evaluation of 1,25(OH)2D3 Effects on FOXP3, ROR-γt, GITR, and CTLA-4 Gene Expression in the PBMCs of Vitamin D-Deficient Women with Unexplained Recurrent Pregnancy Loss (URPL).

Background:Vitamin D insufficiency and deficiency can be associated with adverse effects on fetus and pregnancy outcomes. This study aimed at evaluating the effect of 1,25VitD3 on specific transcription factor and markers of Tregs and Th17 cells in PBMCs of women with URPL as a case group and PBMCs of healthy women as a control group. Methods:Samples from 20 non-pregnant patients with a history of URPL were compared to 20 normal non-pregnant women. PBMCs were divided into three wells for each subject in the presence of 1,25VitD3 (50 nM, for 16 hours), PHA (10 µM; positive control), and without any treatment (negative control). By Real-time PCR (Taqman assay), specific transcription factors of Tregs and Th17 cells, FOXP3, ROR-γt, GITR, and CTLA-4 mRNA expressions in two groups were measured. Results: FOXP3/ ROR-γt mRNA expression in PBMCs decreased significantly in women experiencing URPL compared to the control group (p = 0.0001). Although 1,25VitD3 (50 nM) increased FOXP3 gene expression (p = 0.0001), it did not significantly affect ROR-γt gene expression. Besides, 1,25VitD3 treatment significantly increased FOXP3/ROR-γt mRNA expression from baseline in PBMCs of the fetal loss group compared to that of the control group (p = 0.01). The 1,25VitD3 also increased GITR gene expression (p = 0.017) in PBMCs of URPL women compared to the controls. Conclusion:Vitamin D deficiency may be a contributor to recurrent pregnancy loss and suggests that the supplementation of women with Vitamin D pre-pregnancy may be protective against URPL via affecting Tregs signature genes, FOXP3 and GITR.

Factor XIII Val34Leu polymorphism and risk of recurrent pregnancy loss in Iranian population: a case control study

Recurrent pregnancy loss (RPL) is a heterogeneous condition and thrombophilias have been considered as a probable cause. The aim of this study was to investigate the prevalence of the coagulation factor XIII Val34Leu polymorphism among women with unexplained RPL. A total of 140 women with a history of unexplained RPL and 100 age-matched healthy fertile women were recruited. The presence of FXIII Val34Leu polymorphism among the cases and controls was investigated using PCR-RFLP method. Genotype analyses of the subjects revealed that the patients had a significantly higher prevalence of V/L and L/L than the controls (P<0.05): 33.5% vs. 15%, and 9.2% vs. 2%, respectively. These results indicate a significant association between FXIII Val34Leu polymorphism and unexplained RPL in the Iranian patient.

MTHFR C677T polymorphism contributes to unexplained recurrent spontaneous abortion

Objective To explore the relationship between methylenetetrahydrofolate reductase (MTHFR) 677C>T and unexplained recurrent pregnancy loss (URPL). Methods All patients were recruited from the outpatient department of Obstetrics/Gynaecology & Genetics of Hangzhou First People's Hospital from January 2013 to May 2014.A case-control study was performed.According to the stochastic indicator method, there were 125 subjects with a history of ≥2 times URPL as the case group, and 905 healthy parous women with no history of URPL as the control group.Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to detect the distributions of the polymorphisms of MTHFR 677C>T, and the results were validated using oligo-chip and direct sequencing. Results The allele and genotype frequencies of MTHFR were 60.0% for C, 40.0% for T, 32.0% for CC, 56.0% for CT, and 12.0% for TT in the case group and 67.4% for C, 32.6% for T, 41.4% for CC, 52.0% for CT, and 6.6% for TT in the control group, respectively.The prevalence of allele T was significantly higher in the case group than in the control group (OR=1.379, 95%CI =1.051-1.808, P=0.020), the frequency of genotype TT was also significantly higher in the case group than in the control group (OR=2.344, 95%CI=1.220-4.503, P=0.009). Conclusion The fertile women with MTHFR 677T allele and 677TT genotype may be susceptibility to URPL in a Chinese Han population from the Hangzhou area.(Chin J Lab Med, 2015, 38: 243-246) Key words: Abortion, habitual; 5, 10-Methylenetetrahydrofolate reductase; Genotype; Polymorphism, restriction fragment length; Polymerase chain reaction

Unexplained first trimester recurrent pregnancy loss and low venous reserves

More than half of recurrent pregnancy loss (RPL) remains unexplained. We hypothesized that women with a history of unexplained RPL (URPL) have low venous reserve. Case-control study in 12 women with a history of URPL, 11 healthy nulliparous controls and 12 primiparous controls with a history of uncomplicated pregnancy. To quantify venous reserve, we measured plasma volume (PV, ml/m(2)) and venous compliance in forearm and calf (VC(arm), VC(calf), (ml/dl)/mmHg) during the follicular phase of the menstrual cycle. Mean arterial blood pressure (mmHg) was measured by oscillometry. Arterial demand was evaluated by cardiac index (CI, (l/min)/m(2)). Baseline characteristics were comparable between groups. All groups had similar CI. Women with a history of RPL had 14% and 9% lower mean PV compared with nulliparous and primiparous controls (P < 0.01 and P = 0.04, respectively). In women with URPL, the mean VC(arm) was 25% and 32% lower compared with nulliparous and primiparous controls (P = 0.04 and P < 0.01, respectively), while the mean VC(calf) was 29 and 22% lower compared with the two control groups (P < 0.01 and P = 0.03, respectively). Women with URPL have lower venous reserves when compared with controls at comparable arterial demand. Interventions that increase venous reserve may improve pregnancy outcome.