Risk Of Recurrent Miscarriage Research Articles

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.

M2/ANXA5 haplotype as a predisposition factor in Malay women and couples experiencing recurrent spontaneous abortion: a pilot study

Recurrent spontaneous abortion (RSA) is a prevalent condition among the Malay population of Malaysia, where carriage risk of conventional hereditary thrombophilia factors has been generally ruled out. The contribution of M2/ANXA5, a common haplotype in the annexin A5 gene promoter, was evalauted for RSA in Malay. Seventy-seven women who had experienced two or more unexplained RSA and 41 available male partners were selected for study, with 360 population controls recruited from healthy Malay individuals. Incidence of M2 carriage and odds ratios were calculated between control and patient groups, and clinically defined subgroups and RSA risk was evaluated. M2/ANXA5, found in 42.2% of the general Malay population, was associated with greater risks for women with primary and secondary RSA with early (gestational week 5–15) losses. The risk was somewhat higher in Malay couples when both partners were carriers and a trend of higher prevalence was seen for the male partners patients who had experienced RSA. M2 carriage seems to be a risk factor with unusually high incidence in Malay women and couples with primary and secondary RSA with ‘early’ spontaneous abortions. The associated male partner risk confirms the proposed role of M2/ANXA5 as a genetic trait impeding embryonic anticoagulation.

Role of endothelial nitric oxide synthase gene polymorphisms (Glu298asp) in Egyptian patients with recurrent spontaneous abortion

Background : Previous studies indicated an association between endothelial nitric oxide synthase (eNOS) activity and maintenance of pregnancy, but it is rather controversial whether polymorphisms of the gene encoding for eNOS are associated with recurrent spontaneous abortions (RSAs). Aim: The aim was to investigate whether the presence of maternal polymorphism Glu298Asp in exon seven of the eNOS gene increase the risk of RSA in Egyptian women. Subjects and Methods : Hundreds women were randomly selected as the case group. They had at least three RSA before 20th weeks of gestation, same partner and at least one live birth and compared with 100 women, same age range, with no history of abortions or complicated pregnancy as control group. All were investigated for the polymorphism using the polymerase chain reaction‑restriction fragment length polymorphisms method. Data were expressed descriptively as percentages for qualitative values and mean ± standard deviation for quantitative parametric data and comparison of qualitative data was done. Results : Frequency of GG genotype 50/100% in cases and 67/100% in control group. Heterozygous GT frequency was 46/100% in cases and 26/100% in control (P ≤ 0.01, odds ratio [OR] =2.37, and 95% confidence interval [CI] =1.30–4.34). Homozygous TT was 4/100% in the cases and at 7/100% in control (P = 0.68, OR = 0.77, and 95% CI = 0.21–2.76). GG genotype versus GT and GG (P = 0.01, OR = 2.03, and 95% CI = 1.15–3.60). Cases with TT genotype were more susceptible to abortion at an older age with a mean of 29 (4.76) (P = 0.02). Conclusion : In conclusion, (eNOS) Glu298Asp polymorphism was found to be associated with increased risk of RSA in this sample of Egyptian women. KEY WORDS : Endothelial nitric oxide, polymorphism, recurrent spontaneous abortions, synthase

The importance of MTHFR gene mutation detection in patient with recurrent miscarriages

Homocysteine is an enzyme encoded by MTHFR (methylenetetrahydrofolate reductase) gene located on chromosome 1. Mutations in MTHFR gene may result in the afflicted metabolism of homocysteine and thus might increase the risk of recurrent miscarriages. In some cases, recurrent pregnancy loss could be prevented by prescribing folic acid and B group vitamin supplements. The demand of MTHFR gene sequencing for variations is commonly overlooked by doctors or genetic counsellors. To highlight this problem we present a case study of recurrent miscarriages in a patient with a homozygous c. 655C>T variation in MTHFR gene. Moreover, we discuss the need of molecular genetic testing for MTHFR gene variations in patients with recurrent miscarriages and the treatment of hyperhomocysteinemia.

Evidence for association of the rs605059 polymorphism of HSD17B1 gene with recurrent spontaneous abortions

Objective: To investigate whether the missense rs605059 polymorphism of HSD17B1 gene, which is expressed mainly in the placenta, is associated with recurrent spontaneous abortions (RSA).Methods: This study group consisted of 138 women with three or more unexplained spontaneous abortions, before the 20th week of gestation, with the same partner, while 140 healthy women served as controls. To genotype the individuals, we used the polymerase chain reaction-restriction fragment length polymorphism method.Results: The genotyping of the rs605059 polymorphism revealed the frequencies 0.22, 0.45 and 0.33, for AA, GA and GG genotypes, respectively, for the patient group and 0.37, 0.41 and 0.22, respectively, for the control group. The A allele frequencies were 0.44 and 0.57 for the patient and control group, respectively, and the G allele frequencies were 0.56 and 0.43 for the patient and control group, respectively. Statistical analysis of the results indicated the existence of significant differences in genotype and allele frequencies between the two groups.Conclusion: The rs605059 polymorphism of the HSD17B1 gene is associated with increased risk of RSA in our Caucasian Greek population. Thus it could be used as a prognostic genetic marker for RSA.

Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA)

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type → A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012–2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value = 0.01; odds ratio = 0.25; CI = 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p = 0.60). The A allelic frequency was significantly different between the two groups (p = 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women.

Implication of HLA-G 5′ upstream regulatory region polymorphisms in idiopathic recurrent spontaneous abortions

The effect of HLA-G 5′-upstream regulatory region (URR) single nucleotide polymorphisms (SNP) in idiopathic recurrent spontaneous abortion (RSA) was evaluated. Parental genotype combination analysis and HLA-G expression at transcriptional level was evaluated for 5′URR SNP, which have shown increased risk for idiopathic RSA. If a fetus were aneuploid, attributing causation to a HLA-G 5′-URR SNP would be illogical; therefore couples with abnormal parental karyotypes and also those with abortus material that revealed chromosomal abnormalities were excluded. One hundred women who had experienced idiopathic RSA, along with their respective male partners and 100 pairs of control couples, were studied. HLA-G 5′-URR SNP were evaluated through sequencing. Quantitative polymerase chain reaction was used for HLA-G expression analysis. An increased risk for idiopathic RSA cases among women carriers of mutant genotypes of -1179G>A(rs1233335), -725C>G/T(rs915670) and -486A>C(rs114252012) SNP. The parental genotype combination analysis revealed a 3.5-fold increased risk for -1179G>A and 4.3-fold increased risk for -725C>G/T SNP among carriers of mutant parental genotypes in couples who have experienced idiopathic RSA. Down-regulation in HLA-G expression was seen at transcriptional level for -1179G>A and -725C>G/T SNPs in cases of idiopathic RSA. Transmission of a mutant allele from single carrier parents may, therefore, affect pregnancy outcome.

Polymorphisms in the fibrinolytic pathway genes and the risk of recurrent spontaneous abortion

Impaired fibrinolytic activity is implicated in the pathogenesis of recurrent spontaneous abortion (RSA). This case-control study assessed the prevalence of polymorphisms in fibrinolytic system genes in RSA. Cases comprised 202 Sinhalese women who had experienced at least two first-trimester spontaneous abortions and had no living children; controls were 202 women with no history of spontaneous abortion and two or more living children. The groups were matched for age and ethnicity. DNA was genotyped using the Sequenom MassARRAY system. The PLAUR rs4251923 A (OR 95% CI 2.3 [1.3 to 4.0]), SERBP2 rs6098 A (OR 95% CI 1.4 [1.1 to 1.9]) and SERBP2 rs6103 C alleles (OR 95% CI 1.4 [1.1 to 1.9]) were increased in the RSA group compared with controls. The prevalence of PLAUR rs4251923/ SERBP2 rs6098/ SERBP2 rs6103 GG/AA/CC (OR 95% CI 2.4 [1.2 to 4.9], GA/GA/GC(OR 95% CI 3.9 [1.3 to 11.2]), GA/AA/CC (OR 95% CI 2.9 [1.0 to 8.6] and GA/GG/GG (OR 95% CI 21.3 [1.1 to 410.3]) genotypes were also increased in cases. Polymorphisms in the fibrinolytic system genes are associated with RSA in Sinhalese women. These likely impair implantation.

Antiphospholipid antibodies and the placenta: a systematic review of their in vitro effects and modulation by treatment.

Antiphospholipid antibodies (aPL) are a family of auto-antibodies that are associated with an increased risk of recurrent miscarriage, intrauterine growth restriction and preterm birth. The placenta is a major target of aPL and it is likely that these antibodies promote pregnancy morbidity by affecting trophoblast function. Numerous studies have investigated the effect of aPL on trophoblast function in vitro. However, different trophoblast models and a variety of culture conditions have been employed, resulting in a myriad of different reported findings. This review systematically summarized those published studies that have investigated the effect of aPL on trophoblast function in vitro. In addition, the reported effects of pharmacological treatment on trophoblast function in the presence of aPL were also systematically reviewed. PubMed, Scopus, Embase and Web of Science databases were searched using the keywords 'placenta OR trophoblast' AND 'antiphospholipid antibody OR antiphospholipid syndrome' up to 25 April 2014. Studies were excluded based on the absence of appropriate controls. The effects of aPL on trophoblast proliferation, death, syncytialization, invasion, hormone production, cytokine production, coagulation and complement activation were recorded. The effects of different treatments on the function of trophoblasts in the presence of aPL were also recorded. A total of 1071 records were retrieved from the four databases. After removing duplicates, the titles and abstracts of 529 articles were reviewed. Of those, 48 articles were read and relevant experimental results were extracted from 47 articles. This systematic review provides an overview of all the studies performed to date on the effects of aPL on trophoblast function in vitro. There is considerable support for aPL decreasing trophoblast viability, syncytialization and invasion in vitro. Some work has also suggested that aPL may affect the production of hormones and signalling molecules by trophoblasts, and may stimulate coagulation and complement activation in vitro. Current reports of the in vitro effects of therapeutic treatments on trophoblast function in the presence of aPL are inconclusive. This systematic review has highlighted many gaps in our knowledge of how aPL work and may direct future research in this area.

Association of rs7260002 of chorionic gonadotrophin β5 with idiopathic recurrent spontaneous abortion in Chinese population.

Low levels of serum hCG during the first trimester is regarded as a predictor of miscarriage. This study was designed to examine whether variance in chorionic gonadotrophin β5 (Cgb5) gene confers risk to recurrent spontaneous abortions (RSA) in Chinese women. We recruited a total of 454 RSA subjects and 460 controls from our medical center between the years 2010 to 2013. rs7260002, which resides in the promoter region of Cgb5, was genotyped through direct sequencing. The carriers with the minor allele of rs7260002 had reduced risk of RSA (P = 0.018; P adjusted = 0.032; OR: 0.76; 95 % CI: 0.61-0.96). Genotype frequency was further analyzed under additive, recessive, and dominant models. Significant differences between the RSA subjects and controls were detected under additive and recessive models (P additive = 0.040; P recessive = 0.010). The current study identified a protective allele of the Cgb5 gene against RSA. Functional studies are required to elucidate the effect of the identified SNP on CGB expression and HCG hormone activity.

Platelet-specific collagen receptor glycoprotein VI gene variants affect recurrent pregnancy loss

To determine whether platelet-specific collagen receptor glycoprotein VI (GP6) gene variants are associated with recurrent miscarriages (RM). Genetic association study. Tertiary care referral hospital. A total of 200 women with at least three unexplained spontaneous abortions before 20weeks of gestation and 300 healthy parous women. Determination of variants of GP6 single-nucleotide polymorphisms (SNPs) namely; rs1671153, rs1654410, rs1654419, and rs1613662 was based on polymerase chain reaction-restriction fragment-length polymorphism. Genotypes and haplotypes frequencies were compared in RM case subjects versus control subjects. We observed significantly higher occurrence of rare alleles of SNPs in GP6, namely, rs1671153, rs1654410, rs1654419, and rs1613662, among RM cases, revealing risk association for fetal losses. The synergistic effects of haplotype combinations were also evaluated and showed that four haplotypes G-T-G-G, T-C-A-A, G-C-G-A, and G-T-A-A were more prevalent among RM cases, revealing increased risk for fetal losses. In silico analysis revealed that GP6 has an impact on biologic pathways and significant influence in collagen binding. Gene-gene interaction network analysis revealed that GP6 consisted of a total of 25 interactions with 13 genes in the human genome. These results suggest that variants of GP6 SNPs, namely, rs1671153, rs1654410, rs1654419, and rs1613662, may be associated with risk of recurrent miscarriage. In silico analyses demonstrated the influence of GP6 in biologic pathways, molecular function, including collagen binding, and gene-gene interaction in the human genome.

Gene-gene interactions and risk of recurrent miscarriages in carriers of endocrine gland–derived vascular endothelial growth factor and prokineticin receptor polymorphisms

To study endocrine gland-derived vascular endothelial growth factor (EG-VEGF), prokineticin receptor (PROKR) 1, and PROKR2 variants in the coding regions of idiopathic recurrent miscarriage (RM) patients and further evaluate gene-gene interactions of these three genes. Case-control study. University-based reproductive clinics and genetics laboratory. A total of 142 women with a history of idiopathic RM and 149 control subjects were included. None. All blood samples were nucleotide sequenced in the coding regions of EG-VEGF, PROKR1, and PROKR2. Gene-gene interaction of three gene variants was evaluated with the use of the multifactor dimensionality reduction method. One nonsynonymous variant of each of the three genes was identified, and PROKR1 (I379V) and PROKR2 (V331M) were significantly associated with idiopathic RM. Genetic interactions were found not only between PROKR1 (I379V) and PROKR2 (V331M), but also among EG-VEGF (V67I), PROKR1 (I379V), and PROKR2 (V331M). Women carrying low-risk genotypes had a 77% reduced risk of experiencing miscarriages compared with those carrying high-risk genotypes. The present study corroborates the clinical relevance of the EG-VEGF system in human early pregnancy, and provides evidence for the gene-gene interactions of EG-VEGF and PROKR variants.

Evaluation of the Association between the C677T Polymorphism of Methylenetetrahydrofolate Reductase Gene and Recurrent Spontaneous Abortion

Introduction: One factor known to cause thrombophilia in women with unexplained recurrent spontaneous abortion (RSA) is C677T polymorphism of methylenetetrahydrofolate reductase gene. This study aimed to determine the association between RSA and MTHFR C677T polymorphism in Iranian patients. Methods: In this case-control study, 30 patients with previous history of two or more consecutive unexplained abortions, and 10 women with at least two live births without a miscarriage were analyzed for MTHFR C677T polymorphism using PCR-RFLP (PCR-Restriction Fragment Length Polymorphism) method; the study was carried out on patients referring to Baqiyatallah Hospital and Avicenna Infertility Clinic. The results obtained via estimating the genotype of each polymorphism were analyzed by SPSS version 16. Results: Seventeen women (56.6 %) with recurrent spontaneous abortions and 5 women (50 %) from the control group were heterozygous for MTHFR C677T polymorphism. T-allele frequency in the experiment group was higher than the control group (28.4 % and 25 % for the experiment and control group, respectively). Conclusion: The prevalence of MTHFR C677T polymorphism was slightly higher in RSA patients compared with the controls. This finding failed to support the relationship between this polymorphism and the increasing risk of RSA in the evaluated Iranian women.

Celiac disease and reproductive disorders: meta-analysis of epidemiologic associations and potential pathogenic mechanisms

An increased risk of reproductive failures in women with celiac disease (CD) has been shown by several studies but a comprehensive evaluation of this risk is lacking. Furthermore, the pathogenic mechanisms responsible for obstetric complications occurring in CD have not been unraveled. To better define the risk of CD in patients with reproductive disorders as well as the risk in known CD patients of developing obstetric complications, we performed an extensive literature search of Medline and Embase databases. Odds ratio (OR) and relative risk (RR) with 95% confidence intervals (95% CI) were used in order to combine data from case-control and cohort studies, respectively. All data were analyzed using Review Manager software. In addition, we summarized and discussed the current hypotheses of pathogenic mechanisms potentially responsible for obstetric complications occurring in CD. Patients with unexplained infertility, recurrent miscarriage or intrauterine growth restriction (IUGR) were found to have a significantly higher risk of CD than the general population. The OR for CD was 5.06 (95% CI 2.13-11.35) in patients with unexplained infertility, 5.82 (95% CI 2.30-14.74) in women experiencing recurrent miscarriage and 8.73 (95% CI 3.23-23.58) in patients with IUGR. We did not observe an increased risk of CD in women delivering small-for-gestational age or preterm babies. Furthermore, we found that in celiac patients, the risk of miscarriage, IUGR, low birthweight (LBW) and preterm delivery is significantly higher with an RR of 1.39 (95% CI 1.15-1.67), 1.54 (95% CI 1.22-1.95), 1.75 (95% CI 1.23-2.49) and 1.37 (95% CI 1.19-1.57), respectively. In addition, we observed that the risk for IUGR, LBW and preterm delivery was significantly higher in untreated patients than in treated patients. No increased risk of recurrent miscarriage, unexplained stillbirth or pre-eclampsia was found in celiac patients. In vitro studies have provided two main pathogenic models of placental damage at the feto-maternal interface. On the embryonic side of the placenta, a direct binding of anti-transglutaminase (-TG) antibodies to trophoblast cells and, thus, invasiveness reduction via an apoptotic damage, has been proposed. Anti-TG antibodies may also be detrimental to endometrial angiogenesis as shown in vitro in human endometrial endothelial cells (cultures and in vivo in a murine model). The angiogenesis inhibition seems to be the final effect of anti-TG antibody-mediated cytoskeletal damage in endometrial endothelial cells. Physicians should investigate women with unexplained infertility, recurrent miscarriage or IUGR for undiagnosed CD. Women with CD show an increased risk of miscarriage, IUGR, LBW and preterm delivery. However, the risk is significantly reduced by a gluten-free diet. These patients should therefore be made aware of the potential negative effects of active CD also in terms of reproductive performances, and of the importance of a strict diet to ameliorate their health condition and reproductive health. Different mechanisms seem to be involved in determining placental tissue damage in CD patients.

GSTO1 uncommon genetic variants are associated with recurrent miscarriage risk

To explore the role of the GSTO1 gene in the pathogenesis of recurrent miscarriage (RM). Genetic association study. Rome, Italy. 123 women with RM and 130 women without pregnancy complications. None. Genotyping of two single nucleotide polymorphisms (A140D and E208K) and a 3-bp deletion (E155del) of the GSTO1 gene. We found a statistically significant association between GSTO1*E208K variants and RM risk. Specifically, we identified this uncommon genetic variant only in women with RM. None of the women with physiologic pregnancies were carriers of K208 allele. GSTO1 has a role in detoxification metabolism, and we hypothesize that a functional variation of GSTO1 is a RM risk factor that interacts with environmental conditions.

Glutathione S-transferase A1 polymorphism and the risk of recurrent spontaneous abortion in Chinese Han population

Recurrent spontaneous abortion (RSA) is a multifactor and distressing disease. There are still approximately half of the RSA patients with cause not being identified to date. Accumulating studies have confirmed that genetic polymorphisms in glutathione S-transferases (GSTs) were associated with the risk of recurrent spontaneous abortion. In this study, we aimed to investigate the relationship between the polymorphism of GSTA1, which is GSTA1 -69C/T (rs3957357), and the development of recurrent spontaneous abortion. A case-control study of 127 cases with RSA and 112 ethnic and age matched women as controls was conducted. And measurement of Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) was performed to genotype all of samples in order to analyze the association between GSTA1 -69C/T (rs3957357) and the risk of RSA. We found that the frequencies of genotypes between cases and controls have no significant difference (P = 0.908) and GSTA1 mutant allele GSTA1 -69 T was present at a frequency of 0.122 in case group, while in controls the frequency was 0.125 (P = 0.922). The polymorphism of GSTA1 (rs3957357) may not be associated with the risk of recurrent spontaneous abortion in Chinese Han population.

A proteomic analysis of the endometrium in obese and overweight women with recurrent miscarriage: preliminary evidence for an endometrial defect.

BackgroundOverweight and obese women have been shown to have an increased risk of recurrent miscarriage as well as other adverse reproductive outcomes, but it is yet unclear whether this is due to an effect on the endometrium, embryo or both. The current study employs proteomic analysis to examine for a potential endometrial defect in obese and overweight women with recurrent miscarriage.MethodsProteomic tissue analysis of 21 endometrial samples obtained In the midluteal phase from 16 women with recurrent miscarriage (obese, n = 12 and lean, n = 4) and 5 fertile volunteers (Obese, n = 2 and Lean, n = 3). Proteins were separated using 2-D gel electrophoresis and principle component analysis was used to quantitatively compare protein expression between groups. Protein spots showing significantly altered expression were identified using mass spectrometry.ResultsObese and overweight recurrent miscarriage patients had a significantly increased endometrial expression of haptoglobin compared to their lean counterparts (p = 0.01). These patients also displayed a significant increase in endometrial expression of transthyretin (p = 0.04) and beta- globulin (p = 0.04). Principle Component Analysis (PCA) of the studied groups also demonstrated that endometrial samples could be grouped based on differences in the BMI, suggesting that obesity is an independent factor influencing endometrial protein expression.ConclusionsThese findings provide preliminary evidence for an alteration in the endometrial protein profile in overweight/obese women with recurrent miscarriage mainly in the form of increased haptoglobin, an inflammatory marker associated with obesity.

Significant association between angiotensin-converting enzyme gene insertion/deletion polymorphism and risk of recurrent miscarriage: A systematic review and meta-analysis

BackgroundMany studies have investigated the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and risk of recurrent miscarriage, but the impact is unclear due to inconsistencies among those studies. This study aimed to quantify the strength of the association between ACE I/D polymorphism and recurrent miscarriage risk by performing a systematic review and meta-analysis. Design and MethodsWe searched PubMed, Embase, Web of Science, and Wanfang Medicine databases for eligible articles relating the association between ACE I/D polymorphism and risk of recurrent miscarriage in humans. We estimated the summary odds ratios (ORs) with their 95% confidence intervals (95% CIs) to assess the association. ResultsEleven studies with a total of 3357 individuals were included in this meta-analysis. Compared to the ACE II genotype, DD and ID were both associated with increased risk of recurrent miscarriage (OR DD versus II=1.81, 95% CI 1.23–2.66, P=0.003; OR ID versus II=1.50, 95% CI 1.25–1.80, P<0.001). Sensitivity analyses further confirmed the association above. No evidence of publication bias was observed. ConclusionMeta-analyses of available data show a significant association between ACE I/D polymorphism and recurrent miscarriage risk, and the ACE polymorphic D allele contributes to increased risk of recurrent miscarriage.

Tumor Necrosis Factor-α Gene Polymorphisms in Korean Patients With Recurrent Spontaneous Abortion

The objective of this study was to investigate the contribution of the tumor necrosis factor-α (TNF-α) gene polymorphisms to recurrent spontaneous abortion (RSA). The study participants consisted of 357 Korean women with RSA and 236 fertile women controls. Four TNF-α gene variants of all participants were analyzed by polymerase chain reaction-restriction fragment length polymorphism assay. The TNF-α -1031T>C and TNF-α -238G>A variants increased the risk of RSA TNF-α -1031TC+CC; adjusted odds ratio [AOR], 2.292; 95% confidence interval [CI], 1.547-3.395; P < .001; TNF-α -238GA+AA; AOR, 2.327; 95% CI, 1.038-5.217; P = .040), and these data were not different in a stratified analysis according to the number of consecutive spontaneous abortions. Also, the mutant genotypes of TNF-α -1031 and TNF-α -238 showed synergistic effects on increased RSA risk (-1031TC+CC/-238GA+AA; AOR, 4.054; 95% CI, 1.520-10.812; P = .005). In haplotype analysis, there were similar trends of data for combination analysis. In conclusion, the TNF-α -1031T>C and TNF-α -238G>A variants are possible genetic risk factors for RSA.