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Purpose: The aim of this study was to investigate the potential association of matrix metalloproteinase 7 ( MMP7) -181 A/G and MMP12 -82 A/G functional single nucleotide polymorphisms (SNP) with idiopathic recurrent spontaneous abortion (IRSA) in Slovenian reproductive couples. Methods: A case-control study was conducted on 149 couples with 3 or more consecutive idiopathic spontaneous pregnancy loses and 149 women and men with at least 2 live births and no history of pregnancy complications. Genotyping of MMP7 -181 A/G and MMP12 -82 A/G SNPs was performed using polymerase chain reaction and restriction fragment length polymorphism methods. Results: There were no statistically significant differences in the distribution of MMP7 -181 A/G and MMP12 -82 A/G genotype, allele, or haplotype frequencies between IRSA patients and controls, as well as patients' primary and secondary IRSA. We also found no association of MMP7 -181 A/G and MMP12 -82 A/G genotypes, alleles, and haplotypes with IRSA. Conclusions: We found no evidence to support the association between IRSA and MMP7 -181 A/G and MMP12 -82 A/G SNPs in Slovenian reproductive couples. [ABSTRACT FROM AUTHOR]

Objective. The insulin-like growth factor 2 (IGF2) and its receptor (IGF2R) are important regulators of placental function and fetal growth. Our aim was to investigate the association between IGF2R gene Gly1619Arg G>A polymorphism and recurrent spontaneous abortion (RSA). Methods. Polymerase chain reaction and restriction fragment length polymorphism methods were performed to identify the genotypes in 149 couples with a history of at least three consecutive spontaneous abortions and 149 age-matched, unrelated, and fertile couples. Results. There were no statistically significant differences in genotype or allele frequency among the couples with RSA and healthy controls. Conclusions. We found no evidence that the IGF2R Gly1619Arg variation is associated with RSA. [ABSTRACT FROM AUTHOR]

Objectives: 1) To perform the first comprehensive systematic review of genetic association studies (GASs) in idiopathic recurrent spontaneous abortion (IRSA); 2) to analyze studies according to recurrent spontaneous abortion (RSA) definition and selection criteria for patients and control subjects; and 3) to perform meta-analyses for the association of candidate genes with IRSA.Design: Systematic review and meta-analysis.Setting: Not applicable.Patient(s): Couples with IRSA and their spontaneously aborted embryos.Intervention(s): Summary odds ratios (ORs) were calculated by means of fixed- or random-effects models.Main Outcome Measure(s): Association of genetic variants with IRSA.Result(s): The systematic review included 428 case-control studies (1990-2015), which differed substantially regarding RSA definition, clinical evaluation of patients, and selection of control subjects. In women, 472 variants in 187 genes were investigated. Meta-analyses were performed for 36 variants in 16 genes. Association with IRSA defined as three or more spontaneous abortions (SAs) was detected for 21 variants in genes involved in immune response (IFNG, IL10, KIR2DS2, KIR2DS3, KIR2DS4, MBL, TNF), coagulation (F2, F5, PAI-1, PROZ), metabolism (GSTT1, MTHFR), and angiogenesis (NOS3, VEGFA). However, ORs were modest (0.51-2.37), with moderate or weak epidemiologic credibility. Minor differences in summary ORs were detected between IRSA defined as two or more and as three or more SAs. Male partners were included in 12.1% of studies, and one study included spontaneously aborted embryos.Conclusion(s): Candidate gene studies show moderate associations with IRSA. Owing to large differences in RSA definition and selection criteria for participants, consensus is needed. Future GASs should include both partners and spontaneously aborted embryos. Genome-wide association studies and large-scale replications of identified associations are recommended. [ABSTRACT FROM AUTHOR]

The insertion/deletion (I/D) polymorphism in intron 16 of the angiotensin I-converting enzyme gene ( ACE ) has been extensively studied as a predisposing factor for idiopathic recurrent spontaneous abortion (IRSA). A case-control study including 149 women with ≥3 spontaneous abortions and 149 controls was performed to test the association of ACE I/D polymorphism with IRSA. A systematic review was conducted of previous case-control studies, with strict selection criteria for meta-analyses. We also aimed to evaluate the potential differences in summary estimates between studies defining IRSA as ≥2 and ≥3 spontaneous abortions. Genotyping was performed by PCR, and systematic review conducted using PubMed and Scopus. There was no association of the polymorphism with IRSA in Slovenian women. Sixteen case-control studies, showing substantial differences regarding IRSA definition and selection criteria for women were identified. Meta-analysis was performed and included four studies defining IRSA as ≥2 spontaneous abortions and the current study, which defined IRSA as ≥3 spontaneous abortions. Based on random effects model, meta-analysis conducted on 1192 patients and 736 controls showed no association with IRSA under dominant (DD+IDvsII) and recessive (DDvsID+II) genetic models. Well-designed studies are needed to evaluate the role of ACE I/D polymorphism in IRSA defined as ≥3 spontaneous abortions. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential association of tissue inhibitor of metalloproteinases (TIMP) 1, 2, 3, and 4 gene polymorphisms with idiopathic recurrent spontaneous abortion (IRSA). Design: Case-control and association study. Setting: Departments of gynecology and obstetrics and university-based research laboratory. Patient(s): A total of 149 couples with a history of three or more idiopathic spontaneous pregnancy losses and 149 fertile men and 149 fertile women with at least two live births and no history of pregnancy pathologies. Intervention(s): Polymerase chain reaction and restriction-fragment-length polymorphism methods. Main Outcome Measure(s): Detection of TIMP-1 -372 C/T, TIMP-2 -303 C/T, TIMP-3 -915 A/G, TIMP-3 -1296 C/T, and TIM -3'-UTR C/T genotypes and allele frequencies. Result(s): There were no statistically significant differences in the distribution of any genotype and allele frequencies or any genetic model between IRSA patients and controls. Additionally, no significant associations occurred between combinations of TIMP polymorphisms and the risk of IRSA. Conclusion(s): We found no evidence for the association of TIMP- 1, -2, -3, and -4 with IRSA in a Slovenian population. [ABSTRACT FROM AUTHOR]

Objective: To investigate the potential association of Y chromosome microdeletions with idiopathic recurrent spontaneous abortion (IRSA) in a Slovenian population and compare our results with those of previously published studies in different populations, with the intention of clarifying the potential impact of Y chromosome microdeletions on IRSA. Design: Case–control and association study. Setting: Departments of gynecology and obstetrics and university-based research laboratory. Patient(s): Male partners of 148 couples with at least three spontaneous pregnancy losses of unknown etiology, and 148 fertile men. Intervention(s): Multiplex polymerase chain reactions. Main Outcome Measure(s): Azoospermia factor (AZF) regions were tested for Y chromosome microdeletions according to European Academy of Andrology/European Molecular Genetics Quality Network guidelines. The PubMed database was searched to retrieve articles linking Y chromosome microdeletions and susceptibility to IRSA. Result(s): None of the IRSA or control men had microdeletions in the AZFa, AZFb, or AZFc regions. A total of nine previous studies examined the relationship between Y chromosome microdeletions and IRSA, yielding contradictory results, which we discuss in detail. Conclusion(s): On the basis of our comparisons, it is unlikely that Y chromosome microdeletions contribute to IRSA and are therefore currently not recommended for the routine evaluation of IRSA couples. [Copyright &y& Elsevier]