Gene expression analysis of VEGF and its receptors and assessment of its serum level in unexplained recurrent spontaneous abortion

Unexplained recurrent spontaneous abortion [URSA] is one of the main complications of pregnancy which is usually defined as three or more consecutive pregnancy losses before the 20[th] week of gestation without a known cause. Vascular endothelial growth factor [VEGF] is a potent angiogenic factor and shown, along with its receptors [VEGFR1, 2], to play important roles in several physiologic processes including reproduction. The aim of the present study was to analyze gene expression of VEGF and VEGF receptors in endometrium of patients with a history of URSA compared with normal fertile women. In addition, serum VEGF concentration was assessed and compared between the two groups at the same time. In this case control study, endometrial and blood samples were obtained between day 19[th] and 24[th] of menstrual cycle [window of implantation] from 10 women with a history of URSA [case group] and 6 fertile women who had at least one successful pregnancy [control group]. Expression of VEGF and VEGFRs was studied by reverse transcription- polymerase chain reaction [RT-PCR] and then quantified by real time PCR. Normalization of expression levels was done by comparison with beta-actin expression level as an internal control. Relative VEGF, VEGFR1 and VEGFR2 expression quantities were compared between the two groups. Enzyme linked immunosorbent assay [ELISA] was used for serum VEGF assay. VEGF, VEGFR1 and VEGFR2 gene expression was detected in endometrial samples of both groups. The mean relative expression of VEGF gene was lower in the case group compared with control women, however, both VEGF receptors were expressed higher in endometrium of the case group. In addition, the serum level of VEGF was significantly higher in the case group compared with the controls. Alteration in gene expression of VEGF and its receptors in endometrium and changes of serum VEGF might play important roles in pathogenesis of unexplained RSA

Variations in T-helper 17 and regulatory T cells during the menstrual cycle in peripheral blood of women with recurrent spontaneous abortion

Disorders in immune system regulation may result in pregnancy abnormalities such as recurrent spontaneous abortion [RSA]. This study aims to determine the ratio of regulatory T [Treg] and T helper [Th] 17 cells in unexplained RSA [URSA] women during proliferative and secretory phases of their menstrual cycles compared to healthy non-pregnant women. In this case control study, 25 women with URSA and 35 healthy, non-pregnant women were enrolled. The percentage of Th17 and Treg cells in participants peripheral blood were determined by flow cytometry. The percentage of Th17 cells and their related cytokines in serum [IL-17A] were higher in the proliferative and secretory phases of the menstrual cycles of URSA women compared to the control women. However, a lower percentage of Treg cells and their related cytokines in serum, transforming growth factor [TGF] beta1 and interleukin [IL]-10 were detected in the proliferative but not the secretory phase of the URSA group. The ratio of Th17/CD4+ Treg was higher in the URSA group than the control group. We observed an increased ratio of Th17/CD4+ Treg during the proliferative and secretory phases in URSA women. The imbalance between Th17 and Treg cells during the proliferative phase of menstrual cycles in the URSA group may be considered a cause for spontaneous abortion

Application of plasma exchange in patients with history of unexplained recurrent abortion: a case series

Immune-mediated recurrent pregnancy loss [RPL] has received more attention than any other single etiologic classification. Individuals with rare blood group P have an anti-pp1pk antibody in their serum, which causes recurrent abortion in the early stages. In this case series study, 11 patients with unexplained RPL who had anti-P antibody in their serum were treated by plasma exchange during their next pregnancies. To evaluate the efficacy of the treatment, we monitored fetal development using ultrasonography and intensive prenatal care. All calculations were performed with the SPSS version 16. All patients who were treated by plasma exchange progressed to live birth. The mean gestational age at the time of termination was 37.5 +/- 0.69 weeks. The mean weight of the newborns was 2729.09 +/- 389.88 g. None of the newborns required exchange transfusion. P-incompatibility is one rare but important cause of unexplained RPL and also a basis for therapeutic intervention via early antibody removal by plasma exchange