Risk Of Recurrent Miscarriage Research Articles

曲秀芬教授治疗高龄女性复发性流产经验

复发性流产是育龄期女性临床常见病及流产类疑难病，尤其对于高龄女性因其病因复杂，治疗过程相对困难，更应重视。复发性流产的发生与多种因素有关，但其中有50%原因不明。许多研究显示，自然流产的再发生风险与自然流产的次数有关,高龄亦是复发流产的高危因素。有过1次人工流产的女性发生RSA的风险是没有人工流产的3.28倍。年龄≥40岁的女性发生RSA的风险是年龄<20岁的女性的4.06倍。高龄女性多有手术流产病史及卵巢功能相对较差，故自然流产的风险又相对更高，并且自“二孩”政策开放以来，有意愿生育二孩的女性多，因此高龄女性的围生期治疗显得尤为重要。曲秀芬教授认为，高龄女性复发性流产的病机以肾虚为本，多以肾阳虚为著，兼有肝郁、脾虚、血瘀等。治疗强调标本兼顾，主张“治未病”的思想，孕前调理，培育其损；孕期保胎，固护胎元，且重视高龄女性的心理疏导及生活方式指导，发挥中医治疗此病的优势，既能满足患者的生育要求，又可为国家的生育政策做出突出贡献。 Recurrent spontaneous abortion (RSA), a difficult and complicated disease, is a common disease of the child-bearing age women. Especially for advanced maternal age women, the etiology is complex and difficult to treat, so more attention should be paid. RSA is associated with a variety of factors, but fifty percent of these are unknown. Many studies show that the risk of RSA is related to the number of spontaneous abortions; advanced age is also a high risk factor for RSA. The risk of RSA of women with at least once abortion was 3.28 time of women without abortion. The risk of RSA in women at order age (≥40 years old) was 4.062 time of that younger women (<20 years old). Most advanced age women have a history of surgical abortion, and the function of ovarian is relatively poor, so the risk of RSA is much higher. Since the implement of “the second child” policy, women who wish to have the second child are almost older than 35 years old, so prenatal treatment is particularity important for advanced women. Professor Qu concludes that the etiology and pathogenesis of the disease is the deficiency of the kidney; deficiency of kidney-yang is the main factor, and liver-qi stagnation, spleen deficiency, blood stasis and so on. Treatment emphasizes both the surface and essence, symptomatic treatment should be applied before pregnancy and after pregnant. We pay attention to psychological counseling and lifestyle guidance, give full play to the advantages of traditional Chinese medicine treatment to meet the fertility requirements of patients and make contributions to the national fertility policy.

Interactive Effects of Snps Located Within CD28/B7Pathway and Environment on Susceptibility to Recurrent Spontaneous Abortion

Aims: This study was aimed to explore the interaction between environment and CD28/B7 pathway to provide the potential epidemiology for prevention and treatment of recurrent spontaneous abortion (RSA). Methods: The retrospective study included 630 RSA cases and 1320 healthy women during their middle and late prenatal care. Their living environment was investigated, and the influence of environmental factors on pregnancy abortion was analyzed. The genomic DNAs were extracted from the study subjects, and the polymorphisms of CD28 and B7 were analyzed. Finally, the interaction of gene and environment on RSA was analyzed with the logistic regression analyses. Results: The multi-variate regression analysis indicated that vitamin supplement, intake of fresh fruits or vegetables, night shift, staying up late, history miscarriage, as well as history induced abortion were, independently, risk factors for RSA (all P< 0.05). Moreover, rs3116496 (T>C), rs3181098 (G>A) and rs3181100 (G>C) of CD28, rs1915087 (C>T) of B7-2, as well as rs6804441 (A>G) and rs41271391 (G>T) of B7-1 were correlated with modified RSA risk (all P< 0.05). The haplotypes TGT and TAG could also regulate the risk of RSA (both P< 0.05). The synthetic influences of the aforementioned SNPs and environmental factors could also significantly affect the susceptibility to RSA (all P< 0.05). Conclusion: The interaction of environment and SNPs of CD28/B7 pathway on RSA risk was distinct from CD28/B7 pathway or environment alone.

Evaluation of the adenosine deaminase (ADA) G22A gene polymorphism with recurrent spontaneous abortion among Egyptian patients.

IntroductionAdenosine and deoxyadenosine metabolism is influenced by adenosine deaminase (ADA) enzyme. ADA increases in different diseases and is considered as one of the markers for cell-mediated immunity. Pregnancy is associated with depressed cell-mediated immunity. The level of ADA expression, which seems to play a key role in maintaining pregnancy, is influenced by adenosine deaminase G22A gene polymorphism. We aimed in our study to evaluate the association of ADA G22A gene polymorphism with recurrent spontaneous abortion (RSA) in Egyptian women.Material and methodsAdenosine deaminase G22A gene polymorphism was genotyped in 40 patients (age range 22-39 years) with a history of RSA, selected from those attending the Gynaecology and Obstetrics Clinic of Beni-Suef University Hospital, and 20 age-matched healthy women as a control group, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.ResultsIn our study, no statistically significant difference was found between RSA patients and control group as regards ADA G22A genotypes (p = 0.653) and alleles (p = 0.697). A comparison of the frequencies of ADA alleles in RSA patients as regards the below-35-years-old age group revealed that ADA 2(A) allele was associated with a low risk for RSA in patients aged 35 years old or younger (p = 0.008).ConclusionsIn conclusion, our study revealed an age-dependent protective value of ADA 2(A) allele in recurrent spontaneous abortions among the Egyptian population.

Genetic variant in the CYP19 gene and recurrent spontaneous abortions

BackgroundThe CYP19 gene encodes aromatase, a key cytochrome P450 enzyme that converts androgens to estrogens in the ovarian tissues of premenopausal women. A polymorphic variation C/T in the CYP19 gene, rs10046, results in modified estrogen levels through increasing aromatase activity. In the present study, we investigated the possible association between the rs10046 polymorphism of the CYP19 gene and the risk of recurrent spontaneous abortions (RSA) in the Caucasian Greek population. MethodsIn the prospective case-control study 120 patients and 100 healthy controls were studied. Women who had at least three unexplained spontaneous abortions before 20weeks of gestation were included in the patient group, while the control group consisted of women with at least two successful pregnancies and without history of abortions. The PCR-RFLP method was used in order to genotype the subjects. ResultsThe frequencies of CC, CT, TT genotypes of the rs10046 variant were 0.275, 0.500, 0.225, respectively, in the patient group and 0.210, 0.480, 0.310, respectively, in the control group. The allele frequencies were 0.525 and 0.475 for C and T, respectively, in the patient group and 0.450 and 0.550 for C and T, respectively, in the control group. Statistical analysis of these results indicated that there are no significant differences in genotype (P=0.2897) or in allele frequencies [P=0.1261, OR (95%)=1.351(0.9269–1.969)] between RSA patient and the control groups. ConclusionThe rs10046 polymorphism of CYP19 gene seems that is not an important contributing factor in the aetiology of RSA in the Greek Caucasian population.

Supplementation with progestogens in the first trimester of pregnancy to prevent miscarriage in women with unexplained recurrent miscarriage: a systematic review and meta-analysis of randomized, controlled trials

To investigate whether treatment with progestogens in the first trimester of pregnancy would decrease the incidence of miscarriage in women with a history of unexplained recurrent miscarriage. Systematic review and meta-analysis. Not applicable. Women with a history of unexplained recurrent miscarriage. Randomized, controlled trials were identified by searching electronic databases. We included randomized, controlled trials comparing supplementation with progestogens (i.e., intervention group) in the first trimester of pregnancy with control (either placebo or no treatment) in women with a history of recurrent miscarriage. All types of progestogens, including natural P and synthetic progestins, were analyzed. The primary outcome was the incidence of miscarriage. The summary measures were reported as relative risk (RR) with 95% confidence interval (CI). Ten trials including 1,586 women with recurrent miscarriage were analyzed. Eight studies used placebo as control and were double-blind. Regarding the intervention, two RCTs used natural P, whereas the other eight studies used progestins: medroxyprogesterone, cyclopentylenol ether of progesterone, dydrogesterone, or 17-hydroxyprogesterone caproate. Pooled data from the 10 trials showed that women with a history of unexplained recurrent miscarriage who were randomized to the progestogens group in the first trimester and before 16weeks had a lower risk of recurrent miscarriage (RR 0.72, 95% CI 0.53-0.97) and higher live birth rate (RR 1.07, 95% CI 1.02-1.15) compared with those who did not. No statistically significant differences were found in the other secondary outcomes, including preterm birth (RR 1.09, 95% CI 0.71-1.66), neonatal mortality (RR 1.80, 95% CI 0.44-7.34), and fetal genital abnormalities (RR 1.68, 95% CI 0.22-12.62). Our findings provide evidence that supplementation with progestogens may reduce the incidence of recurrent miscarriages and seem to be safe for the fetuses. Synthetic progestogens, including weekly IM 17-hydroxyprogesterone caproate, but not natural P, were associated with a lower risk of recurrent miscarriage. Given the limitations of the studies included in our meta-analysis, it is difficult to recommend route and dose of progestogen therapy. Further head-to-head trials of P types, dosing, and route of administration are required.

Effect of miRNA-27a and Leptin Polymorphisms on Risk of Recurrent Spontaneous Abortion.

BackgroundThe aim of this study was to investigate the possible associations of miRNA-27a and Leptin polymorphisms with the risk of recurrent spontaneous abortion (RSA).Material/MethodsBetween May 2013 and April 2015 at Shenzhen Longhua New District Central Hospital, we randomly recruited 138 RSA patients as the case group and another 142 normal pregnancy women as the control group. We used denaturing high-performance liquid chromatography (DHPLC) to determine the genotypes and allele frequencies of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A.ResultsThe GG genotype and G allele frequencies of miRNA-27a rs895819 A/G were higher in the case group than in the control group, and the AA genotype and A allele frequencies of Leptin rs7799039 G/A were also higher in the case group than in the control group (all P<0.05). MiRNA-27a rs895819 A/G and Leptin rs7799039 G/A polymorphisms increased the risk of RSA (Exp (B)=2.732, 95% CI=1.625~4.596, P=0.000; Exp (B)=4.081, 95% CI=1.817~9.164, P=0.001). GG-AA or AG-AA carriers had a higher risk of RSA. The miRNA-27a expression of AA carriers of miRNA-27a rs895819 was lower than that of AG+GG carriers both in the case and control groups (all P=0.024). The plasma leptin concentration of GG carriers was lower than that of GA+AA carriers in the case group (P=0.026).ConclusionsThe polymorphisms of miRNA-27a rs895819 A/G and Leptin rs7799039 G/A may contribute to an increased risk of RSA.

Association of interleukin-10 gene promoter polymorphisms with recurrent miscarriage: a meta-analysis.

The association between IL-10 gene promoter polymorphisms and the risk of recurrent miscarriages (RM) remains controversial. The present meta-analysis was performed to derive a precise estimate of the relationship. We searched the PubMed and EMBASE for studies related to the association between the IL-10 gene polymorphism and the risk of RM. Summary odds ratio (OR) with 95% confidence interval (CI) was estimated to assess the associations. Thirteen studies, including 2047 RM cases and 2055 control samples, were identified. The results showed a significant association between rs1800896, rs1800871 and RM risk (for rs1800896: GA+GG vs AA: OR=1.20, 95% CI=1.04-1.39, P=.02; for rs1800871: CT+TT vs CC: OR=1.64, 95% CI=1.13-2.36, P=.009). No evidence of association was noted between rs1800872 haplotype and RM risk. IL-10 gene promoter polymorphisms, rs1800896 and rs1800871, play a potential role in increasing the risk of RM.

Risk of Recurrent Miscarriage in India and the Effect of Paternal Age and Maternal Age

&lt;div&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Background:&lt;/em&gt;&lt;/strong&gt;&lt;em&gt; A risk of miscarriage increases with increase in parental age. However many studies investigate only the effect of maternal age. This study focused on both the maternal age and paternal age effect on miscarriage.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Method:&lt;/em&gt;&lt;/strong&gt;&lt;em&gt; Couples with the pregnancy loss issue were studied with the age range 19 to 50 years. Maternal age and paternal age were analyzed together. The couples composed of a women and man both aged 20-29 years were used as reference group.&lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Results:&lt;/em&gt;&lt;/strong&gt;&lt;em&gt; Universally the risk of miscarriage was found to be higher if the women age was 35 years or more and man with age was 40 years or more. But due to small sample size this has not been proved in this study. &lt;/em&gt;&lt;/p&gt;&lt;p&gt;&lt;strong&gt;&lt;em&gt;Conclusions:&lt;/em&gt;&lt;/strong&gt;&lt;em&gt; The risk of pregnancy loss increases if male and female partners are having advanced age.&lt;/em&gt;&lt;/p&gt;&lt;/div&gt;

Association between HLA-E gene polymorphism and unexplained recurrent spontaneous abortion (RSA) in Iranian women

Human leukocyte antigen-E (HLA-E)is a non-classical major histocompatibility complex (MHC) class I antigens which expressed on extra villous cytotrophoblast, which interacts with NKG2A, is an inhibitory receptor on natural killer (NK) cells and leading to down regulation of immune response in the maternal-fetal interface and provides maternal immune tolerance of the fetus. This study was designated to investigate the gene frequencies of E0101 and E0103 in HLA-E gene in Iranian women with recurrent spontaneous abortion (RSA). Amplification Refractory Mutation System (ARMS-PCR) technique was carried out to detect polymorphism in exon 3 of the HLA-E gene in women with RSA and controls (n=200). Differences between groups were analyzed by SPSS19 software using (2) test. There was no significant difference in the allele frequencies of the HLA-E polymorphism between RSA and fertile controls but HLA-E 0101/0103 heterozygous genotype was found to be significantly higher in RSA group (p=0.006, OR=1.73), so this genotype might confer susceptibility to RSA. Our results suggest that HLA-E 0101/0103 heterozygous genotype leads to increase of RSA risk. It seems that by genotyping of HLA-E polymorphism, we can predict the risk of RSA in infertile women.

Association between p53 polymorphism at codon 72 and recurrent spontaneous abortion.

p53 gene plays an important role in apoptosis, which is necessary for successful invasion of trophoblast cells. The change from an arginine (Arg) to a proline (Pro) at codon 72 can influence the biological activity of p53, which predisposes to an increased risk of recurrent spontaneous abortion (RSA). In order to investigate the association between p53 polymorphism at codon 72 and RSA, we conducted this meta-analysis. Pubmed, Embase and Web of science were used to identify the eligible studies. Odds ratio (OR) with 95% confidence interval (CI) was used to evaluate the strength of the association. Six studies containing 937 cases of RSA and 830 controls were included, and there was one study deviated from Hardy-Weinberg equilibrium (HWE). There was a significant association between p53 polymorphism at codon 72 and RSA in recessive model (Pro/Pro vs. Pro/Arg+Arg/Arg; OR=1.60, 95% CI: 1.14-2.24) and co-dominant model (Pro/Pro vs. Arg/Arg; OR=1.47, 95% CI: 1.02-2.12) whether the study that was deviated from HWE was eliminated or not. A significant association was observed in allelic model (Pro vs. Arg; OR=1.28, 95% CI: 1.04-1.57) after exclusion of the study that was deviated from HWE. No association was noted in recessive model (Pro/Pro+Pro/Arg vs. Arg/Arg; OR=1.05, 95% CI: 0.86-1.30) and co-dominant model (Pro/Arg vs. Arg/Arg; OR=0.96, 95% CI: 0.77-1.19). Subgroup analysis by ethnicity also indicated a significant association between p53 polymorphism at codon 72 and RSA in Caucasian group. No heterogeneity and publication bias were found. Our meta-analysis implied that p53 polymorphism at codon 72 carries high maternal risk of RSA.

An Association Study of the SLC19A1 Gene Polymorphisms/Haplotypes with Idiopathic Recurrent Pregnancy Loss in an Iranian Population.

The genetics of folate metabolism is one of the most significant mechanisms influencing fetal growth and may underlie some cases of unexplained recurrent miscarriage. Reduced folate carrier 1, encoded by the SLC19A1 gene, is a transporter of folate. Folate deficiency and elevated levels of homocysteine could be disadvantageous for the female reproductive system health. Thus, the balance between homocysteine and folate status can be used to measure the risk of recurrent pregnancy loss. The purpose of this study was to determine the association between -43T>C, 80G>A, and 696C>T polymorphisms of the SLC19A1 gene in 147 women who had unexplained recurrent miscarriage in comparison with 150 healthy women. Amplification refractory mutation system-polymerase chain reaction was used to genotype the molecular polymorphisms of this gene. The results indicated that the -43T>C single nucleotide of the SLC19A1 gene was significantly associated with a risk of recurrent miscarriage in Iranian women (p < 0.05). No significant association was observed for the other two polymorphisms. The haplotype frequency distribution of -43C/80G/696C, -;43C/80G/696T, -43C/80G, and 80G/696T was significantly different in patients than controls, which may represent a novel risk factor for idiopathic recurrent pregnancy loss. Polymorphisms and haplotypes of the SLC19A1 gene can be considered risk factors for idiopathic recurrent pregnancy loss.

Annexin A5 haplotype M2 is not a risk factor for recurrent spontaneous abortion in Northern Europe: is there sufficient evidence?

The M2 haplotype of the annexin A5 gene is a well-recognized predisposition factor for recurrent spontaneous abortion (RSA). A recent publication by Nagirnaja et al. (2015) in PLoS One discusses the risk role of the M2 haplotype for RSA in cases compared with controls of North European extraction and arrives at a negative result. As a number of previous and fairly recent studies have supported the proposed involvement of the M2 haplotype in the cause of idiopathic RSA, this commentary aims to highlight problematic issues in the above publication. It is the opinion of the authors that the study by Nagirnaja et al. (2015) does not generate adequate proof of the absence of RSA risk, attributable to carriage of the M2 haplotype.

A SNP in pri-miR-10a is associated with recurrent spontaneous abortion in a Han-Chinese population.

MicroRNA-10a (miR-10a) has a wide range of functions in nearly all mammalian tissues and is involved in the occurrence of many diseases. However, it remains unknown whether miR-10a is associated with human recurrent spontaneous abortion (RSA). In this study, we found that rs3809783 A > T in miR-10a coding region was significantly associated with the increase of the risk of human unexplained RSA (URSA) acquisition in a Han-Chinese population. The T allele of rs3809783 hindered the production of mature miR-10a. A to T substitution in miR-10a rs3809783 repressed cell proliferation and migratory capacity. Further investigation discovered that Bcl-2-interacting mediator (Bim) was the functional target of miR-10a and inversely regulated Bim expression. Dual-luciferase assay indicated that A allele in miR-10a rs3809783 could more effectively suppress Bim expression than T allele. In addition, A to T substitution in miR-10a rs3809783 attenuated the sensibility of cells to progesterone and its antagonist mifepristone. Collectively, our data suggest that rs3809783 A > T in pri-miR-10a may be conductive to the genetic predisposition to RSA by disrupting the production of mature miR-10a and reinforcing the expression of Bim.

MIR17HG Gene Polymorphism and the Risk of Recurrent Spontaneous Abortion

Background: Recurrent pregnancy loss (RPL) is two or more consecutive pregnancy losses before 20 weeks of gestation. So far the disease is known for a variety of reasons, but still about 50% of recurrent pregnancy losses are unknown. The miRNAs are a family of 20 - 25 nucleotide RNA that inhibit translation of the target gene or mRNA degradation and play a key role in a variety of regulatory pathways. The miRNA is involved in embryonic developments and regulatory disorders which cause numerous diseases including heart diseases and pregnancy-associated disorders. Recent studies suggest that common genetic factors may exist between ischemic heart disease and abortion. Objectives: The current study aimed to investigate the relationship between rs6492538 polymorphism of MIR17HG gene and recurrent spontaneous abortion, which might be clinically useful as a marker to assess risks for recurrent pregnancy loss to provide good health care during pregnancy. Materials and Methods: The case and control groups were studied for the association between polymorphism of MIR17HG and recurrent pregnancy loss in Iranian females. One-hundred patients with recurrent abortions (at least two) as cases and one-hundred healthy female with two or more normal term deliveries and without a history of abortion were selected as controls. Total genomic DNA was isolated from blood leukocytes. SNPs were studied with Alu1 as a restriction enzyme. Results: Results of the present study indicated significant association between rs6492538 polymorphism and recurrent pregnancy loss (P > 0.05). Conclusions: The results of the present study provide evidence for association between genetic variation in MIR17HG and recurrent spontaneous abortion. Further studies will be required to validate the significance of the studied genetic variation in diverse populations and its regulatory role on target genes.

Investigation of the Annexin A5 M2 haplotype in 500 white European couples who have experienced recurrent spontaneous abortion

Annexin A5 is a placental anti-coagulant protein that contains four nucleotide substitutions (M2 haplotype) in its promoter. This haplotype is a risk factor for recurrent spontaneous abortion (RSA). The influence of the M2 haplotype in the gestational timing of spontaneous abortions, paternal risk and relationships with known risk factors were investigated. European couples (n = 500) who had experienced three or more consecutive spontaneous abortions, and two fertile control groups, were selected for this study. The allele frequency of M2 was significantly higher among patients who had experienced early RSA than among controls (P = 0.002). No difference was found between controls and patients who had undergone late spontaneous abortions. No difference was found between patients who had experienced RSA who had a live birth or no live births, or between patients who were positive or negative for known risk factors. Male and female partners in each group had similar allele frequencies of M2. The M2 haplotype is a risk factor for early spontaneous abortions, before the 12th week of gestation, and confers about the same relative risk to carriers of both sexes. Having one or more M2 allele(s) in combination with other risk factors further increases the RSA risk.

Higher urinary bisphenol A concentration is associated with unexplained recurrent miscarriage risk: evidence from a case-control study in eastern China.

BackgroundEvidence about the association between Bisphenol A (BPA) and the risk of recurrent miscarriage (RM) in human being is still limited.ObjectiveWe evaluated the association of urinary BPA concentrations with RM in human being.MethodsA hospital-based 1:2 matched case-control study on RM was carried out in Suzhou and Kunshan in Jiangsu Province in China between August 2008 and November 2011. Total urinary BPA concentrations in 264 eligible urine samples (102 RM patients and 162 controls) were measured using liquid chromatography-tandem mass spectrometry (LC-MS/MS). The Wilcoxon test and conditional logistic regression were used to estimate the differences between the groups and odds ratios (OR) with 95% confidence intervals (CI), respectively.ResultsThe median ± IQR (interquartile range) (P 75-P 25) values of non-creatinine-adjusted total urinary BPA levels in the RM patients and the controls were 1.66±3.69ng/ml and 0.58±1.07ng/ml, respectively (0.98±2.67μg/g Cr (creatinine) and 0.40±0.77μg/g Cr. The adjusted BPA level was significantly higher in the RM patients than in the controls (Wilcoxon test, Z = 4.476, P<0.001). Higher level of urinary BPA was significantly associated with an increased risk of RM (P-trend <0.001). Compared to the groups with urinary BPA levels less than 0.16μg/g Cr, the women with levels of 0.40–0.93μg/g Cr and 0.93μg/g Cr or above had a significantly higher risk of RM (OR = 3.91, 95%CI: 1.23–12.45 and OR = 9.34, 95%CI: 3.06–28.44) that persisted after adjusting for confounding factors. The time from recently RM date to recruitment does not significantly influence the urinary BPA level (P = 0.090).ConclusionExposure to BPA may be associated with RM risk.

The obesity-related FTO gene variant associates with the risk of recurrent miscarriage.

To investigate the association of the fat mass and obesity associated gene (FTO) rs9939609 single nucleotide polymorphism with recurrent miscarriage. Candidate gene association study. Human Genetics Unit, Colombo, Sri Lanka. A total of 202 Sinhalese women with two or more first-trimester miscarriages and no living children (cases) and 202 age- and ethnicity-matched women with no history of miscarriage and having two or more living children (controls). Peripheral blood was collected from the participants and DNA was extracted. Genotyping was performed at the Australian genome Research Facility using the Sequenom MassARRAY system. Genotype and allele frequencies of cases were compared with controls using chi-squared testing. The prevalence of the single nucleotide polymorphism in cases and controls. The mean age of the women in the recurrent miscarriage group was 31.9 ± 0.4 years and that of the control group was 32.3 ± 0.3 years. Of the women in the recurrent miscarriage group, 140 (69.3%) had experienced three or more first-trimester miscarriages. The prevalence of the AA genotype [p = 0.0002, odds ratio (95% CI) = 3.8 (1.8-8.0)] and A allele [p = 0.002, odds ratio (95% CI) = 1.6 (1.2-2.2)] of the FTO rs9939609 single nucleotide polymorphism were increased in women in the recurrent miscarriage group compared with the control group. The obesity-related FTO rs9939609 single nucleotide polymorphism associates with recurrent miscarriage. This finding warrants further investigation with controlling for important factors such as body mass index, diabetes and cardiovascular disease status. The single nucleotide polymorphism may be useful in predicting the risk of recurrent miscarriage.

Association of VEGF genetic polymorphisms with recurrent spontaneous abortion risk: a systematic review and meta-analysis.

BackgroundStudies of the associations between the genetic polymorphisms of the vascular endothelial growth factor (VEGF) gene and recurrent spontaneous abortion (RSA) have revealed conflicting results. The present meta-analysis was performed to provide a more precise estimation of these relationships and to explore potential sources of heterogeneity that may have influenced the reported disparities.MethodsAn extensive literature search for relevant studies was conducted on PubMed, Embase, and The Cochrane Library through June 6, 2014. Crude odds ratio (OR) with 95% confidence intervals were calculated.Results10 case-control studies including 1,832 RSA patients and 2,271 healthy controls were identified. Meta-analysis indicated that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms in the VEGF gene correlated with elevated RSA risk. The rs1570360 variant was statistically significantly relevant to RSA risk among non-Asian populations. Interestingly, the rs3025039 variant was statistically significantly relevant to RSA risk among Asian populations.ConclusionsThe current meta-analysis indicates that rs1570360, rs3025039, rs2010963, and rs3025020 polymorphisms increase RSA susceptibility. Moreover, rs1570360 and rs3025039 polymorphisms may play various roles in RSA susceptibility in various geographic groups.

Genetic association between FXIII and β-fibrinogen genes and women with recurrent spontaneous abortion: a meta- analysis.

FXIII Val34Leu (rs5985) and β-fibrinogen -455G/A (rs1800790) genotypes have been reported to be associated with recurrent spontaneous abortion (RSA). However, this topic is controversial. This study aimed to explore whether FXIII Val34Leu or β-fibrinogen -455G/A gene polymorphisms are related to RSA. In this analysis, PubMed, HuGENet and Chinese National Knowledge Infrastructure (CNKI) databases were reviewed. Four models including the dominant model (Val/Val+Val/Leu vs. Leu/Leu), recessive model (Val/Val vs Val/Leu + Leu/Leu), co-dominant model (Val/Val vs. Val/Leu, Val/Val vs. Leu/Leu) and per-allele analysis (Val vs. Leu) were applied. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the association between RSA and FXIII Val34Leu and β-fibrinogen -455G/A polymorphisms. Nine studies with 10 sets of data were included according to the inclusion criterion. A positive association was detected in the pooled results for the dominant model (Val/Val+Val/Leu vs. Leu/Leu; OR = 0.417, 95% CI: 0.180-0.965, I(2) = 45.60%) and co-dominant model (Val/Val vs. Val/Leu; OR = 0.638, 95% CI: 0.452-0.899, I(2) = 36.40%) for FXIII Val34Leu polymorphisms. However, no statistically significant association between β-fibrinogen -455G/A polymorphisms and RSA was detected in the four different models, including the Asian and Caucasian subgroup analyses. Our meta-analysis demonstrates that the FXIII Val34Leu polymorphism has a close association with RSA and women who carry the Val allele for the FXIII Val34Leu polymorphism could have a protective effect against RSA. However, no association is detected between β-fibrinogen -455G/A polymorphisms and the risk of RSA. Future well-designed studies are needed to confirm these results.

A single nucleotide polymorphism in the MTOR gene is associated with recurrent spontaneous abortion in the Chinese female population

Recurrent spontaneous abortion (RSA) is a multi-factor disease. The mammalian target of the the rapamycin (MTOR) gene has been reported to be involved in mouse embryo development and regulates the proliferation of embryonic stem cells. Our study explored the relationship between the single nucleotide polymorphism (SNP) rs17027478 in the promoter region of MTOR gene and the development of RSA. A total of 306 patients with RSA and 127 healthy females as the controls were recruited in the case-control study. The predesigned TaqMan SNP Genotyping Assay was adopted to analyze the association between rs17027478 and the development of RSA. Quantitative real-time reverse transcription polymerase chain reaction and luciferase reporter assays were conducted to analyze the function of the variant. It was found that a significant association exists between the variant and the risk of RSA among the patients who experienced no less than three spontaneous abortions (p = 0.043). However, the significant difference disappeared among the total samples (p = 0.524). Furthermore, we observed lower MTOR mRNA levels in the blood of RSA patients compared with healthy females (p = 0.020). The luciferase reporter assay showed that the rs17027478A allele significantly reduced the luciferase activity (p = 0.029). The results demonstrated that the variant rs17027478 in the promoter region of MTOR might be a good candidate responsible for the pathogenesis of RSA.