Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: prospective cohort study

Ricci, Giuseppe; Bogatti, P.; Fischer-Tamaro, L.; Giolo, Elena; Luppi, Stefania; Montico, Marcella; Ronfani, Luca; Morgutti, Marcello

doi:10.1093/humrep/der261

Cited by 43 publications

(24 citation statements)

References 52 publications

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“…Mutation carrier women may have a more favorable uterine for implantation. Consistent with our study, Ricci et al [28] found that IR were not significantly different between carrier and non-mutation carrier women before and after adjustment for female age, infertility diagnosis and the number of IVF cycles. Thus, we conclude that inherited thrombophilias did not affect embryo implantation.…”

Section: Discussionsupporting

confidence: 92%

“…No article was obtained with manual retrieval. Finally, 7 articles [14][15][16][17][18][19][20] were included in this meta-analysis (Table 1). These included studies were published between 2007 and 2015 with the ages of subjects between 30.9 and 36.2.…”

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

“…Meanwhile, 2 articles [15,20] reported FVL mutation with good heterogeneity (I 2 = 92.0 %, P = 0.0006) and no significant difference (RR = 1.57, 95 % CI 0.55-4.47, P = 0.40) were observed. In addition, one article [20] reported MTHFR (A1298C) (RR = 1.01, 95 % CI 0.93-1.10, P = 0.77), one [20] reported PGM (RR = 0.83, 95 % CI 0.63-1.10, P = 0.20) and one [16] reported FVL/PGM (RR = 1.31, 95 % CI 0.82-2.09, P = 0.26), and no significant differences of these mutation were found between the two groups.…”

Section: Merging Quantitative Datamentioning

confidence: 99%

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Association between in vitro fertilization outcomes and inherited thrombophilias: a meta-analysis

Tan

Sao

et al. 2016

J Assist Reprod Genet

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Purpose The aim of this study was to determine whether in vitro fertilization (IVF) outcomes are associated with inherited thrombophilias. Methods Several databases including PubMed, Embase, and Cochrane Library were retrieved up to 12 January 2016. The quality of the included studies was assessed by two authors. The associations of the following mutations in inherited thrombophilias and IVF outcomes were explored: factor V Leiden (FVL), prothrombin gene G20210A mutation (PGM), 5,10-methylentetrahydrofolate reductase (MTHFR) C677T, MTHFR (A1298C) and activated protein C resistance (APCR). The main outcome measures included CPR and implantation rate (IR). The relative risk (RR) and its 95 % confidence interval (CI) were calculated for effect index. Heterogeneity test was evaluated by Chi-square based on Q statistic and I 2 statistics. Results A total of seven articles published between 2007 and 2015 with the ages of subjects between 30.9 and 36.2 were included. For subgroups analysis of CPR or IR, there were no significant differences in MTHFR (C377T), MTHFR (A1298C), FVL, PGM, and FVL/PGM mutation were found between the mutation group and control group (P > 0. 05). Conclusions IVF outcomes are not associated with FVL, PGM, MTHFR (C677T), MTHFR (A1298C), and APCR mutation in inherited thrombophilias.

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Section: Discussionsupporting

confidence: 92%

Section: Characteristics Of Included Studiesmentioning

confidence: 99%

Section: Merging Quantitative Datamentioning

confidence: 99%

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Association between in vitro fertilization outcomes and inherited thrombophilias: a meta-analysis

Tan

Sao

et al. 2016

J Assist Reprod Genet

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“…It is for these reasons FII and FV genes mutations are the first priority in SNP analysis panel presented. Contrary to this point of view, there are some evidences that the presence of pathological alleles in FII and FV genes in general does not affect the outcome of IVF [8,25]. It is noted that despite an increase in the frequency of FII and FV gene mutations, especially in combination, in patients with ovarian hyperstimulation syndrome, is not effective to carry out a total screening before IVF from an economic point of view [7].…”

Section: Snp In Blood Coagulation Factors Genes Which Were Included Imentioning

confidence: 97%

Toward optimal set of single nucleotide polymorphism investigation before IVF

Ivanov

Dedul

Fedotov

et al. 2016

Gynecological Endocrinology

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Background: At present, the patient preparation for IVF needs to undergo a series of planned tests, including the genotyping of single nucleotide polymorphism (SNP) alleles of some genes. In former USSR countries, such investigation was not included in overwhelming majority of health insurance programs and paid by patient. In common, there are prerequisites to the study of more than 50 polymorphisms. An important faced task is to determine the optimal panel for SNP genotyping in terms of price/number of SNP. Materials and methods: During 2009-2015 in the University Hospital of St. Petersburg State University, blood samples were analyzed from 550 women with different reproductive system disorders preparing for IVF and 46 healthy women in control group. In total, 28 SNP were analyzed in the genes of thrombophilia factors, folic acid cycle, detoxification system, and the renin-angiotensin system. The method used was real-time PCR. Results: A significant increase in the frequency of pathological alleles of some polymorphisms in patients with habitual failure of IVF was shown, compared with the control group. As a result, two options defined panels for optimal typing SNP before IVF were composed. Standard panel includes 8 SNP, 5 in thromborhilic factors, and 3 in folic acid cycle genes. They are 20210 G4A of FII gene, R506Q G4A of FV gene (mutation Leiden), -675 5G44G of PAI-I gene, L33P T4C of ITGB3 gene, -455 G4A of FGB gene, 667 C4T of MTHFR gene, 2756 A4G of MTR gene, and 66 A4G of MTRR gene. Extended panel of 15 SNP also includes 807 C4T of ITGA2 gene, T154M C4T of GP1BA gene, second polymorphism 1298 A4C in MTHFR gene, polymorphisms of the renin-angiotensin gene AGT M235T T4C and -1166 A4C of AGTR1 gene, polymorphisms I105V A4G and A114V C4T of detoxification system gene GSTP. Conclusion:The results of SNP genotyping can be adjusted for treatment tactics and IVF, and also medical support getting pregnant. The success rate of IVF is increased as the result, especially in the group with the usual failure of IVF.

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“…The results of this review were inconclusive, since the methodological quality of studies was poor, many were retrospective case-control, known to be limited by poor collection of data D. Khalife, G. Ghazeeri Open Journal of Obstetrics and Gynecology on potential confounders and recall bias [49]. Ricci has confirmed the absence of association of thrombophilia with adverse IVF outcome by conducting a prospective cohort study of 510 women to compare the prevalence of factor V leiden and prothrombin gene G20210A mutation in women undergoing IVF and showed no statistical significant difference in the reproductive outcomes (implantation rate (IR), clinical pregnancy rate (CPR), and livebirth rate (LBR)) compared to non-mutation carrier women [43]. These findings were supported also by a retrospective study of 594 women reporting that screening for hypercoagulability is not warranted as it does not improve reproductive outcomes [44], and a cohort study of 70 patients that showed no differences in the incidence of factor V leiden, prothrombin and MTHFR mutations in patients with repeated failure (5.9% vs 2.8%, 0%vs 5.6% and 35.3% vs 50%) [45].…”

Section: Thrombophilia and Ivfmentioning

confidence: 98%

Recurrent Implantation Failure and Low Molecular Weight Heparin

Khalife¹,

Ghazeeri²

2018

OJOG

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Implantation of the embryo into the endometrium is the first step in the establishment of pregnancy. This process is complex, and depends on many factors. Recurrent implantation failure is a source of distress to patients and specialists. It is defined as failure to achieve a viable pregnancy, following ">3 embryo transfers with high quality embryos or the transfer of ≥ 10 embryos in multiple transfers". Thrombophilic conditions that contribute to recurrent implantation failure are the main concern in this review. The mechanism of implantation failure is believed to be due to decreased blood flow to the endometrium and placenta which can hinder normal endometrial receptivity leading to miscarriage. Defects in early placentation resulting in pregnancy failure, have focused attention on the therapeutic potential of low molecular weight heparin in the implantation process. Heparin has a role at all stages of implantation to improve pregnancy outcomes. There are controversies in literature regarding the association between thrombophilia and recurrent implantation failure and available literature regarding this issue is very heterogeneous. Various investigators, have shown that women with RIF are more likely to have a thrombophilia disorder, yet a clear cause cannot be acknowledged from these studies. Heparin treatment has been evaluated in several studies, showing conflicting evidence. However, several studies have pointed out that it may play a role in a subset of patients who presents a thrombophilia mutation, thus the group of patients that might benefit is needed to be identified. This review is dedicated to evaluate the published literature about the role of low molecular weight heparin in case of recurrent implantation failure with or without the presence of thrombophilia.

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Factor V Leiden and prothrombin gene G20210A mutation and in vitro fertilization: prospective cohort study

Cited by 43 publications

References 52 publications

Association between in vitro fertilization outcomes and inherited thrombophilias: a meta-analysis

Association between in vitro fertilization outcomes and inherited thrombophilias: a meta-analysis

Toward optimal set of single nucleotide polymorphism investigation before IVF

Recurrent Implantation Failure and Low Molecular Weight Heparin

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