Unexplained Recurrent Abortion Research Articles

Effects of Compound Xuanju Capsule on T Lymphocyte Subsets in Patients With Unexplained Recurrent Abortion

Objective: To investigate the effect of compound Xuanju capsule on T lymphocyte subsets in patients with unexplained recurrent abortion. Methods: The effect of compound Xuanju capsule for the treatment of unexplained recurrent abortion wasinvestigated in a randomized, single blind and clinical trial with control of prednisone and lymphocyte immunotherapy. 211 patients were randomly divided into three groups which were given compound Xuanju capsule, prednisone, and lymphocyte immunotherapy respectively. The main outcome measures were T lymphocyte subsets (T lymphocyte ratio, Th cell ratio, Ts cell ratio, Th/Ts cell ratio, NK cell ratio) whichwas detected in the three groups before and after treatment (at the end of one course of treatment) and the secondary outcome measure was TCM syndrome grade andpregnancy outcome. Results: (1) T lymphocyte subsets: Compared with beforetreatment, the Total T cell ratio showed no significant difference (P>0.05) in the threegroups. The Th cell ratio was lower (P<0.01) in the three groups and the decrease of Thcell ratio in compound Xuanju capsule group and prednisone group was moresignificant than that in the immunotherapy group (P < 0.01). The Ts cell ratio was higher in compound Xuanju capsule group and prednisone group (P < 0.05). The Th/Ts cellratio was lower in the three groups (P < 0.05) and the decrease of Th/Ts cell ratio incompound Xuanju capsule group and prednisone group was more significant than thatin the immunotherapy group (P < 0.05). Total proportion of NK was lower (P<0.001) in the compound Xuanju capsule group and prednisone group. The Total NK cell ratioshowed no significant difference (P > 0.05) in the immunotherapy group (P > 0.05). (2)Pregnancy outcome: Pregnancy outcomes were significantly improved but there wasno significant difference (P > 0.05) in the three groups. (3) TCM syndrome grade:Compared with before treatment, the TCM syndrome grade was lower (P<0.05) in the Copyright © 2024 Cognizant Communication Corp.Acupuncture & Electro-therapeutics Research E-pubthree groups and the decrease of TCM syndrome grade in compound Xuanju capsulegroup was more significant than that in the prednisone group and immunotherapy group(P < 0.01). Conclusion: Compared with before treatment, the Th cell ratio, Th/Ts cellratio and Total NK cell ratio was lower and the Ts cell ratio was higher in compoundXuanju capsule group. Pregnancy outcomes of patients were significantly improved.Compound Xuanju capsule is superior to prednisone and lymphocyte immunotherapywhen it comes to TCM syndrome grade reduction. These results suggest that CompoundXuanju Capsule can regulate the immune function of unexplained recurrentspontaneous abortion (URSA) patients, suppress abnormal immune response, and playa certain role in the treatment of recurrent abortion with unknown causes

Research progress of immune balance and genetic polymorphism in unexplained recurrent abortion

The etiology of recurrent spontaneous abortion (RSA) is extremely complex, as there are 40–50% of patients with unexplained miscarriages, known as unexplained RSA (URSA). URSA affects approximately 1–2% of females of childbearing age and has a massive impact on the physical and mental conditions of both patients and their families. The pathogenesis of the disease remains unclear, making its treatment complicated. In recent years, considerable progress has been made in the exploration of the URSA immune balance mechanism and it has been universally acknowledged that a balanced immune response (as abnormal immunity) may be the root cause of poor pregnancy outcomes. This review discussed and summarized the effects of immune cells and blocking antibodies (BAs) on URSA based on the current state of knowledge in this area. Additionally, molecular genetics also plays an essential role in the incidence rate of URSA since the role of genetic polymorphism in the pathogenesis of URSA has been thoroughly studied. Nonetheless, the outcomes of these studies are inconsistent, particularly across populations. This paper reviewed previous studies on URSA and maternal genetic polymorphism, focusing on and synthesizing the most important findings to date, and providing diagnostic recommendation for URSA patients with clinical symptoms.

Retracted: Study on the Relationship between Unexplained Recurrent Abortion and HLA-DQ Gene Polymorphism.

[This retracts the article DOI: 10.1155/2022/8005538.].

Effects of different doses of estrogen on ER expression and ovarian function in patients with unexplained recurrent abortion

Study design: Randomized trial. Objective: This study was designed to investigate the effects of different doses of estrogen on the expression of estrogen receptor (ER) in endometrial tissue and ovarian function in patients with unexplained recurrent spontaneous abortion (URSA). Methods: Eighty-eight patients with URSA in our outpatient department were randomly divided into three groups. They were treated with estradiol valerate (EV); standard dose of 4 mg/d (31 cases), high dose of 6 mg/d (27 cases) and 9 mg/d (30 cases). Progesterone was detected in the luteal phase, ovarian ovulation during follow-up treatment and the next month after drug withdrawal. ER expression in intima of EV 4 mg group, EV 6 mg group, and EV 9 mg group was detected by immunohistochemistry and PCR was performed before and 3 months after the treatment. Results: Anovulation of 88 URSA patients during hormone treatment was found as follows: 5 cases in the EV 4 mg group, 18 cases in the EV 6 mg group, 25 cases in the EV 9 mg group; Anovulation in the next month after drug withdrawal: 1 case in EV 4 mg group, 8 cases in EV 6 mg group, and 16 cases in EV 9 mg group. After stratified and grouped analysis, the expression of intimal ER in the EV 4 mg group, EV 6 mg, and EV 9 mg groups was significantly increased compared to before treatment in the 3 groups after treatment compared to before treatment (p < .05). There was no significant difference in ER expression between the three groups before and after treatment (p > .05). Conclusion: The higher the therapeutic dose of estrogen, the stronger the inhibition of ovarian ovulation, and the standard dose of estrogen has obvious advantages in increasing the expression of ER in intima. Limitation: 1) Insufficient sample size; 2) We need to increase the sampling time point to further observe the difference of estrogen in time effect, so as to obtain a more accurate action time of estrogen; 3) The longer-term effects of different doses of estrogen on intima were not studied, such as whether there are adverse pregnancy outcomes such as preterm birth, placental implantation, or premature exfoliation.

Study on the Relationship between Unexplained Recurrent Abortion and HLA-DQ Gene Polymorphism.

Objective The study aimed to investigate the relationship between human leukocyte antigen (HLA-DQB1) gene variants and recurrent miscarriage. Methods HLA-DQ gene polymorphisms (PCR-SSP) were detected in 50 couples with recurrent miscarriage (URSA group) and 30 couples with normal births (control group) using sequence-specific primer-guided polymerase chain reaction. Results The frequency of the DQB1∗0303 allele in the URSA group (21.50%) was substantially higher than that of the control group (11.67%) (P=0.0260 0.05, RR = 1.754); however, the frequency of the DQB1∗0302 allele in the URSA group (4.00%) was substantially lower than that of the control pair (10.00%) (P=0.0318 0.05, RR = 0.400); the frequency of sharing one allele was 46.00% (23/50) in the URSA group and 0.00% (0/30) in the normal control group; the frequency of sharing two alleles was 40.00% (2/50) in the URSA group and 43.33% (13/30) in the normal control group, with no significant difference between the two groups. Conclusion For the Zhejiang population, HLA-DQB1∗0303 may be a susceptibility gene for recurrent miscarriage, while HLA-DQB1∗0302 may be protective against recurrent miscarriage, especially for women.

Research update for the immune microenvironment of chronic endometritis

Chronic endometritis (CE) is a persistent and subtle local inflammatory disease characterized by abnormal plasma cell infiltration in the endometrial stroma.The incidence of chronic endometritis is as high as 15–57.5% in women suffering from infertility, implantation failure of in vitro fertilization (IVF) and unexplained recurrent abortion. Many studies both at home and abroad have shown that CE can reduce the receptivity of endometrium and affect embryo implantation. According to the existing reproductive immunity research, the abnormality of immune cell subsets in endometrium is an important factors leading to pregnancy failure. The immune microenvironment in endometrium consists of immune cells and immune molecules, and their influence on embryo implantation can not be ignored. This review paper discusses the controversy of pathogenesis, diagnosis and treatment of CE from the perspective of immune microenvironment by referring to related literature at home and abroad, and investigates the possible ways to improve the diagnosis and treatment of CE.

Ayurvedic Management of Putraghani Yonivyapada (Recurrent Abortions): A Case Report

Recurrent miscarriages are characterized as three or more spontaneous abortions in a row before the 20th week. In the majority of instances, genetic factors, immunological and endocrine factors, infection, and unknown causes are the most common causes of first trimester abortion. Hormonal therapy, heparin injection, and immunotherapy are the available treatments. In this case study, the patient had three abortions during the first trimester. Because all of the tests came out normal, the diagnosis of unexplained recurrent abortions was made. For 40 days before conception, the patient was treated with Ayurvedic medications such as Indukanta Ghrita, Phalghrita. The patient was conceived with these drugs, and later Phalaghrita and other medicines were given for the duration of the pregnancy. Ayurvedic medicine is an effective way to deal with recurring abortions.

Does LIN28B gene dysregulation make women more likely to abort?

BackgroundLIN28B 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).MethodsThe 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.ResultsThe 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.ConclusionsLIN28B 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 summaryPropagation 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.

Effect of immunotherapy on patients with unexplained recurrent spontaneous abortion.

At present, it is generally believed that immune factors account for 60% of unexplained recurrent spontaneous abortion (URSA). The treatments used for URSA depend on immunomodulation for their effects, and paternal immunization, intravenous immunoglobulin, and the use of growth factors such as granulocyte-colony stimulating factor (filgrastim) have been shown to have a beneficial effect on patients with a poor prognosis. However, these treatment schemes and effects remain controversial. This study aimed to evaluate the effect of immunotherapy using lymphocyte active immunotherapy (LAI) on patients with URSA, and to provide evidences for the clinical effect of this treatment. The detailed data of total 619 patients with URSA were collected and analyzed, of which 465 patients (LAI group) with immunotherapy and 154 patients (control group) without immunotherapy. After 77.6% of all the patients in LAI group received the immunotherapy, the maternal blocking antibody (BA) was changed from negative to positive. The conversion rate of maternal BA was increased as the increase of active immunization (>4 times, P<0.05). The pregnancy rate of LAI Group was higher than that of the control group (P<0.05), and there were significant differences of live rate and abortion rate (P<0.05). In addition, compared with the natural pregnancy, the live rate was higher, and the abortion rate was lower in in vitro fertilization (IVF) patients after active immunization, although the difference was not significant (P>0.05). After lymphocyte immunotherapy, most of the patients with unexplained recurrent spontaneous abortion had the positive BA instead of negative BA. Whether the BA was converted or not, the pregnancy rate and live rate were increased, and the abortion rate was decreased after immunotherapy. Therefore, active immunotherapy could improve the pregnancy outcome of the patients with unexplained recurrent abortion.

4 Sperm, but not seminal plasma, elicit changes in the bovine endometrial transcriptome after natural mating

Studies in mice and pigs have shown that seminal plasma (SP) can modulate the uterine environment, leading to an increase in embryo survival and implantation. However, in cattle, conflicting evidence has resulted from studies in which SP was infused into the uterus. In contrast to mice and pigs, it is questionable whether any SP reaches the bovine uterus during natural mating. However, sperm could act as vehicle for SP proteins that bind to their plasma membrane at ejaculation. Thus, the aim of this study was to analyse the effect of exposure to SP, in the presence or absence of sperm, on the endometrial transcriptome. Beef heifers were oestrus synchronized and mated after being seen in standing oestrus with intact bulls (which ejaculate sperm and SP, n=7) or vasectomized bulls (VX, which only ejaculate SP, n=8) or left unmated (control, n=7). To reduce a potential bull effect, 3 vasectomized and 2 intact Holstein bulls were used. Each heifer was mounted once to one intact or VX bull. Heifers were slaughtered 24h (±6h) after mating, and their reproductive tracts were recovered. Endometrial tissue from the base of the uterine horn ipsilateral to the ovulatory follicle was processed for RNA sequencing. Surprisingly, mating with a VX bull resulted in no differentially expressed genes (DEG) in the endometrium compared with unmated controls. In contrast, mating with intact bulls resulted in 22 DEG (10 down regulated and 12 upregulated) compared with unmated controls and 24 DEG (6 downregulated and 18 upregulated) compared with VX samples. The upregulated genes in intact versus VX samples included several that may have a potential role in implantation: CX3CL1, C4BPA, VCAM1-like, and IL17F. Gene CX3CL1 promotes trophoblast migration in women and has been described as a potential bovine embryokine. In addition, decreased levels of C4BPA have been correlated with implantation failure and unexplained recurrent abortions in women. Further, VCAM1 is involved in bovine conceptus implantation and is downregulated in women with unexplained infertility. In mice, SP regulates inflammation of IL17F in the uterus through the γδT/IL-17 pathway. On the other hand, the immune-related genes PRSS2 and CEBPD were downregulated in intact versus control samples, and BOLA-DQB was downregulated in intact versus VX samples. Gene PRSS2, involved in tissue remodelling, is upregulated in the endometrium of repeated breeder cows. Gene CEBPD, is a transcription factor that enhances IL6 expression, whereas BOLA-DQB is involved in antigen presentation. Interestingly, the gene coding for the α-chain of this protein is also downregulated in high fertility cows. In conclusion, these results do not support a direct effect of SP in regulating pregnancy success in cattle. However, sperm can elicit modest endometrial transcriptomic changes related to implantation and immune system regulation. Further research is needed to elucidate the role of intrinsic sperm proteins, or SP proteins transported by these cells, in the modulation of the uterine environment. This work was supported by EU Horizon 2020 Marie Sklodowska-Curie (No. 792212).

Reproductive complications in celiac disease patients in Slovenia

ObjectiveCeliac disease is associated with higher risk of infertility, recurrent abortions, and adverse outcomes in pregnancy and in puerperium. The aim of the study was to analyse the association between celiac disease and reproductive disorders in the group of celiac patients and compare these to healthy controls. MethodsA retrospective case-control matched study. The association between celiac disease and menstrual cycle, gyneco-obstetrical complications was assessed with a questionnaire specifically developed for the study. 144 celiac women and 61 celiac men, members of Slovenian Celiac Society, together with 71 healthy women and 31 healthy men participated in the study. ResultsA higher percentage of celiac women (27.1%) had difficulties in conception of the first child when compared to healthy controls (12.7%) (p = 0.042). In addition, celiac women experienced more complications than healthy controls during the pregnancy, such as abortions or intrauterine growth retardation (p < 0.005). In our study, the prevalence of reproductive problems was not the same in celiac males and females. Altogether 2 celiac men (3.3%) reported having fertility problems, however, the difference between male cases and controls was not statistically significant (p = 0.548). ConclusionPhysicians should examine women with unexplained infertility, recurrent abortions or intrauterine growth retardation for undiagnosed celiac disease. Compared with healthy women, women with celiac disease have increased risk of spontaneous abortions, preterm delivery and fewer successful pregnancies.

Decidual Interleukin-22-Producing CD4+ T Cells (Th17/Th0/IL-22+ and Th17/Th2/IL-22+, Th2/IL-22+, Th0/IL-22+), Which Also Produce IL-4, Are Involved in the Success of Pregnancy.

Trophoblast expressing paternal HLA-C resembles a semiallograft, and could be rejected by maternal T cells. IL-22 seems to be involved in allograft rejection and thus could be responsible for miscarriages. We examined the role of decidual IL-22-producing CD4+ T on human pregnancy. In those experiencing successful pregnancy and those experiencing unexplained recurrent abortion (URA), the levels of IL-22 produced by decidual CD4+ T cells are higher than those of peripheral blood T cells. We found a correlation of IL-22 and IL-4 produced by decidual CD4+ T cells in those experiencing successful pregnancy, not in those experiencing URA. The correlation of IL-22 and IL-4 was also found in the serum of successful pregnancy. A prevalence of CD4+ T cells producing IL-22 and IL-4 (Th17/Th2/IL-22+, Th17/Th0/IL-22+, Th17/Th2/IL-22+, and Th0/IL-22+ cells) was observed in decidua of those experiencing successful pregnancy, whereas Th17/Th1/IL-22+ cells, which do not produce IL-4, are prevalent in those experiencing URA. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells are exclusively present at the embryo implantation site where IL-4, GATA-3, IL-17A, ROR-C, IL-22, and AHR mRNA are expressed. T-bet and IFN-γ mRNA are found away from the implantation site. There is no pathogenic role of IL-22 when IL-4 is also produced by decidual CD4+ cells. Th17/Th2/IL-22+ and Th17/Th0/IL-22+ cells seem to be crucial for embryo implantation.

Advances in Understanding the Immune Imbalance between T-Lymphocyte Subsets and NK Cells in Recurrent Spontaneous Abortion.

Recurrent spontaneous abortion is a global problem, and unexplained recurrent abortion triggered by immunological factors is an important focus of current research. Helper T lymphocytes (Th cells) and regulatory T lymphocytes (Treg cells) are central in human immune regulation and play a complex role in pregnancy. Natural killer cells (NK cells) exist in the endometrium and cooperate with T lymphocytes to create immune tolerance at the maternal-fetal interface, which is essential for successful pregnancy. This review has analyzed studies on Th17 cell, Treg cell and NK cell dysfunction and cellular imbalances which may contribute to unexplained recurrent spontaneous abortion to suggest a possible direction for future immunotherapies.

Low transcriptional activity of PON2 in recurrent abortion: A novel therapeutic agent?

ObjectiveOxidative stress has been reported to be associated with various pregnancy complications and to play key roles in many of them. An inadequate level of antioxidant defense may eventually lead to an early pregnancy loss. There is a lack of information about the roles of the PON2 and PON3 enzymes in the etiology of the cases of unexplained recurrent abortus. The aim of our study is to determine and present the data regarding the roles of these enzymes for the first time. Materials and methodsWe measured the transcriptional levels of the PON2 and PON3 enzymes in the curettage materials obtained from the patients with unexplained recurrent abortus (n=25) and compared the results with those measured in the abortus materials from healthy pregnant women (n=50) who had undergone a voluntary abortion. The transcriptional activities of PON2 and PON3 enzymes were measured through quantification of their respective mRNAs by RT-qPCR assay. For each gene, 2−ΔCt replication values of the control and the patient groups were compared using the Student's t-test, and the p values were calculated thereafter. Fold-changes in the enzyme transcription levels were interpreted as up- or down-regulation. ResultsPON2 mRNA expressions were found to be highly decreased in the patient group (p=0.000002). PON3 transcription, when compared to the healthy pregnant women, was found to be down-regulated in the patient group; however, the difference was not statistically significant (p=0.69). ConclusionsIn this study, we evaluated the expressional regulation of the PON2 and PON3 enzymes in unexplained recurrent abortus. Our results demonstrate for the first time that the expressions of PON2 and PON3 are down-regulated in the abortion specimens of the patients with recurrent miscarriage. Although both enzymes had low expression levels, the decrease in the transcriptional activity of PON2 revealed a high statistical significance. According to these results, it is rational to speculate that PON2 may be a novel therapeutic agent in the management of the cases with unexplained recurrent abortion.

Low dose Cyclosporin A treatment increases live birth rate of unexplained recurrent abortion - initial cohort study

Pregnancy is similar to allogeneic transplantation. Eighty percent of unexplained recurrent spontaneous abortions (URSA) relate to disturbances of immune regulation. Cyclosporin A (CsA) is a immunosuppressant widely used after organ transplantation and to treat autoimmune disease. Animal studies show that low dose of CsA could induce maternal-fetal immunity tolerance while enhance trophoblast invasion. So far no clinical trial reported on the effect and safety of cyclosporin A treatment for URSA has been published. The objective of this study was to explore the effect, safety, and mechanism of low-dose CsA treatment in human patients in order to find a novel therapy to treat URSA. Eighty-six patients with eligible URSA treated at the clinic of the present hospital were included in this study from December 2009 to December 2012. The research was approved by the Ethics committee. Through a clinical study with prospective non-randomized controlled trials, the patients were divided into CsA treatment group (n = 66 cases) and in control group (n = 20 cases) based on the patients' choice. Both groups started treatment as soon as the pregnancy test was positive. Patients in the treatment group were treated with oral CsA 100 mg/day for 30 days. Patients in the control group were treated with progesterone 20 mg im per day until 12 weeks of gestation. Cytoimmunology test of CD3, CD4, CD8, CD4/8, CD4/25, CD19/21, and Th/Ts were examined before and after the treatment in both groups. Clinical consequences of mothers and fetuses were followed up and recorded. Live birth rate and cytoimmunology markers and their change before and after the treatment were analyzed and compared between the two groups. The live birth rate was significantly higher in study group (41/66, 62.1%) than in the control group (6/20, 30.0%) (p < 0.001). There was no obvious side effect and adverse consequence in the pregnancy women. No IUGR or birth defect was observed in fetus in this study. After CsA treatment, CD3 level in maternal blood was higher in successful group than abortion group but CD8 level was decreased after CsA treatment. Low-dose CsA treatment increases live birth rate of unexplained recurrent abortion. No maternal-fetal adverse consequence was observed in this study and it is safe in clinic use. The mechanism of CsA therapy may be related to immune regulation which may favor the success of pregnancy.

Studies on the Infants Born to the Patients with Unexplained Recurrent Abortion Who Underwent Immunotherapy using their Husband’s Lymphocytes

Studies on the Infants Born to the Patients with Unexplained Recurrent Abortion Who Underwent Immunotherapy using their Husband’s Lymphocytes

Role of oxidant-antioxidant balance on incidence of unexplained recurrent spontaneous abortion at first trimester of pregnancy

The present study was aimed to investigate one of the causes for unexplained recurrent spontaneous abortion at first trimester of pregnancy by determining the levels of Oxidative stress (Malondialdehyde) and determine the levels of Antioxidant defense system(Superoxide dismutase, Trolox equivalent antioxidant capacity, Total Antioxidant Capacity)on pregnant women with unexplained recurrent spontaneous abortion at first trimester of pregnancy compared with control group, as well as study the relationship between maternal age and the incidence of recurrent spontaneous abortion .This study has been accomplished using 60 of blood samples of women in Baghdad and have been divided into 50 pregnant women with unexplained recurrent spontaneous abortion at first trimester of pregnancy (patients) and 10 pregnant women at first trimester of pregnancy without any history of recurrent abortion (control).The results of statistical analysis of the present study showed: There was a significant increase in percentage and number of incidence of abortion with Aging of pregnant women who had unexplained recurrent spontaneous abortion at first trimester of pregnancy compared with control group and the highest percentage was found in women age greater than 35 years (47.368%) of more than four cases of occurrences Unexplained Recurrent Abortion at first trimester of pregnancy .There was a significant increase (P≥0.05) in level of MDA in pregnant women with unexplained recurrent abortion at first trimester of pregnancy compared with control group, and there was a significant decrease(p ≤ 0.05) in level of Antioxidant SOD , TEAC , TAC in patients compared with control group .

The role of prophylactic use of low dose aspirin and calheparin in patients with unexplained recurrent abortion

Objective: To study the effect of prophylactic use of low dose aspirin and heparin on patients with recurrent unexplained pregnancy loss.Methods: Prospective case control study conducted on 180 pregnant women randomized into two equal groups. Group 1 received low-dose aspirin 75 mg and heparin 5000 IU subcutaneous every 12 h. Group 2 received no treatment.Results: There was a statistically significant difference between the two study groups regarding number of patients who completed their first trimester (66 versus 39) (p values 0.018). The outcome regarding completion of first trimester was not related to age, BMI or number of previous abortions in both the study groups. Complications of the use of aspirin calheparin occurred in 60% of the patients. The most common complication was bruising at injection site occurring in 60% of the patients followed by bleeding gums (14.4%), gastrointestinal troubles (12.2%), epistaxis (10%) and transient thrombocytopenia in only 2.22% of the patients (Table 4).Conclusion: The use of prophylactic dose of calheparin and aspirin is associated with increased chance of passing 1st trimester safely regardless the age, body mass index or number of abortion in women with unexplained recurrent spontaneous abortion.

Interleukin-17-producing decidual CD4+ T cells are not deleterious for human pregnancy when they also produce interleukin-4.

BackgroundTrophoblast expressing paternal HLA-C antigens resemble a semiallograft, and could be rejected by maternal CD4+ T lymphocytes. We examined the possible role in human pregnancy of Th17 cells, known to be involved in allograft rejection and reported for this reason to be responsible for miscarriages. We also studied Th17/Th1 and Th17/Th2 cells never investigated before. We defined for the first time the role of different Th17 subpopulations at the embryo implantation site and the role of HLA-G5, produced by the trophoblast/embryo, on Th17 cell differentiation.MethodsCytokine production by CD4+ purified T cell and T clones from decidua of normal pregnancy, unexplained recurrent abortion, and ectopic pregnancy at both embryo implantation site and distant from that site were analyzed for protein and mRNA production. Antigen-specific T cell lines were derived in the presence and in the absence of HLA-G5.ResultsWe found an associated spontaneous production of IL-17A, IL-17F and IL-4 along with expression of CD161, CCR8 and CCR4 (Th2- and Th17-type markers) in fresh decidua CD4+ T cells during successful pregnancy. There was a prevalence of Th17/Th2 cells (producing IL-17A, IL-17F, IL-22 and IL-4) in the decidua of successful pregnancy, but the exclusive presence of Th17 (producing IL-17A, IL-17F, IL-22) and Th17/Th1 (producing IL-17A, IL-17F, IL-22 and IFN-γ) cells was found in the decidua of unexplained recurrent abortion. More importantly, we observed that Th17/Th2 cells were exclusively present at the embryo implantation site during tubal ectopic pregnancy, and that IL-4, GATA-3, IL-17A, ROR-C mRNA levels increased in tubal biopsies taken from embryo implantation sites, whereas Th17, Th17/Th1 and Th1 cells are exclusively present apart from implantation sites. Moreover, soluble HLA-G5 mediates the development of Th17/Th2 cells by increasing IL-4, IL-17A and IL-17F protein and mRNA production of CD4+ T helper cells.ConclusionNo pathogenic role of decidual Th17 cells during pregnancy was observed. Indeed, a beneficial role for these cells was observed when they also produced IL-4. HLA-G5 could be the key feature of the uterine microenvironment responsible for the development of Th17/Th2 cells, which seem to be crucial for successful embryo implantation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12948-016-0039-y) contains supplementary material, which is available to authorized users.

Clinical significance of nonspecificity of antiphospholipid antibodies in recurrent abortions and unexplained infertility.

Background:Antiphospholipid antibodies (APLA) are acquired autoantibodies directed to phospholipids which are associated with slow progressive thrombosis and infarction of placenta. Infertility and recurrent pregnancy loss may occur because of impaired trophoblast function, placental infarction, and abnormal blood clotting.Aim:To evaluate APLA (IgG and IgM) in cases of infertility and recurrent abortions.Materials and Methods:A prospective study comprising 70 subjects was carried out. Fifty cases of unexplained infertility and recurrent abortions (25 each) constituted the study group. Twenty healthy multipara females of same reproductive age group constituted the control group. Venous blood samples were collected, and serum was analyzed for two types of APLA (IgG and IgM) by ELISA method.Results:The mean IgM and IgG levels in recurrent abortions group were 8.10 MPL-U/ml and 6.17 GPL-U/ml, respectively whereas in control group, the levels were 4.67 MPL-U/ml and 4.53 GPL-U/ml, respectively. The difference was statistically nonsignificant. The mean IgM and IgG levels in unexplained infertility group were 7.30 MPL-U/ml and 6.12 GPL-U/ml, respectively whereas in control group, the levels were 4.67 MPL-U/ml and 4.53 GPL-U/ml, respectively. Again the difference was statistically nonsignificant.Conclusions:The present study concludes that there is no significance of raised APLA in cases of infertility and recurrent abortions.