A Research On The Genetical Etiology Of Recurrent Pregnancy Loss And A Meta-analysis On Studies Of The Association Between Factor V Leiden And Recurrent Pregnancy Loss

Objective: To detect the genetic etiology of recurrent pregnancy loss and the application of SNP-array in diagnosing recurrent pregnancy loss.Material and methods: Collect the products of conception from recurrent pregnancy loss patients in outpatient department and inpatient department from Jan.2012to Jan.2014. Use SNP-array technique to find out the causes of RPL.Results:Ten samples were analyzed, including2samples with normal chromosomes and8with abnormal chromosomes. Of the8samples with abnormal chromosomes, five (62.5%) were numerical abnormal, all of them were trisomies, including one No.2chromosme trisomy, one No.13chromosme trisomy, one No.21chromosme trisomy and two No.22chromosme trisomies; five (62.5%) were structure abnormal, including3chromosomes with fragment deletion and2chromosomes with uniparental disomy; two (25%) samples contained both numerical and structural abnormalities, one was No.22choromosome trisomy and No.11chromosome with UPD, and the other was No.13chromosome trisomy and No.10chromosome with microdeletionl.Conclusion: The abnormalities of chromosomes are the most common etiology of RPL, while the autosome trisomy is the most frequently recognized reason in genetic etiology. SNP-array technique is highly accurate with high resolution, it provide a more advanced method to detect the etiology of RPL. Objective: To detect and discuss the relationship between factor V Leiden and recurrent pregnancy loss.Methods:The authors identified the literatures that research the association of factor V Leiden with unexplained recurrent pregnancy loss using the PubMed, Embase, Vip and Wanfang online database. The authors search and screen the literatures separately according to the inclusion criteria and exclusion criteria. Then the extracted data were documented into the standard designed table. Finally we use the RevMan5.2software to carry out the meta-analysis.Results:There were21literatures totally included. In the overall analysis, the FVL G1619A GA, AA, GA+AA genotypes and the frequence of A allele, the risk leading to RPL in case group was significantly higher than that in control group, and the OR values were2.12(95%CI,1.70-2.64; P<0.00001),5.59(95%CI,1.84-16.96; P=0.002),1.84(95%CI,1.34-2.54; P=0.0002),1.79(95%CI,1.24-2.59).In the subgroup analysis, in the aspect of ethnicities, in Caucasian, the FVL G1619A AA, GA, GA+AA and the frequence of A allele, the association with RPL was also significantly higher in case group than that in control group, the OR values were1.98(95%CI,1.51-2.60; P<0.0001),1.75(95%CI,1.22-2.49; P<0.002)1.70(95%CI,1.12-2.57; P=0.01); in AA genotype, the relationship was also higher in case group than in control group but was not significant. In mixed ethnicities, the FVL G1619A AA, GA+AA genotypes were much more relevant to RPL in case group, and the difference was significant, the only one literature about AA revealed that OR87(95%CI,12-627;P<0.001)., to analyze the A allele frequence, in case group the risk of RPL was higher but there’s no significance,OR value was1.97(95%CI,0.97-4.00; P=0.06). In view of the period of RPL in pregnancy, in1st trimester, the FVL G1619A GA, AA, GA+AA and the frequence of A allele, all have much higher risk of RPL in case group than in control group, the OR values were1.77(95%CI， 1.18-2.65; P=0.006),9.51(95%CI,2.23-40.56; P=0.002),1.79(95%CI,1.13-2.86; P=0.001),1.71(95%CI,1.05-2.79;P=0.03), and the differences were all significant. In2nd trimester, the FVL G1619A GA, GA+AA genotypes and the frequence of A allele, the risk of RPL were significantly higher, OR values were4.91(95%CI,3.24-7.45; P<0.00001),5.81(95%CI,3.85-8.74; P<0.0001),3.83(95%CI,1.92-7.62; P=0.0001), one literature was on AA genotype, the OR value was168(95%CI,22-879; P＜0.0001)Conclusions:We can conclude from our meta-analysis that, there’s a strong relationship between FVL and URPL. The GA genotype has a2-fold risk of RPL, while in AA genotype it could reach5.6-fold; the carriers of A allele had a risk of nearly2-fold. At the same time, we found that although there was inherited heterogenicity in this mutation, both the Caucasian and mixed ethnicities owning the mutation were related to URPL, and the risk in mixed ethnicity was higher. In1st and2nd trimester of pregnancy, FVL also could lead to RPL, and in2nd trimester the risk was higher. Due to the multifactor that cause RPL, it is necessary to screen other risk factors that result RPL.