Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis

Wen, Yanfei; He, Haodong; Zhao, Kai

doi:10.1007/s10815-023-02823-x

Cited by 6 publications

(3 citation statements)

References 136 publications

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“…Furthermore, it could represent a risk factor for residual venous occlusion after idiopathic DVT [26]. Additionally, the PAI-1 4G/5G polymorphism is significantly involved in the development of RPL by altering metabolic, thrombotic, and immune factors, as shown by multiple studies [27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Impact of Thrombophilic Polymorphisms in Antenatal Women on Perinatal Health: A Single-Center Prospective Study

Sokol Karadjole,

D’Amato,

Milošević

et al. 2024

JPM

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Background: Despite pregnancy’s hypercoagulable state, the correlation between inherited thrombophilia and thrombotic adverse pregnancy outcomes remains uncertain. The objective of this study was to determine the prevalence of inherited thrombophilic polymorphisms among asymptomatic pregnant individuals and to examine their potential correlation with adverse perinatal outcomes. Methods: in this single-center prospective study, 105 healthy pregnant women were included. Genotyping was conducted for factor V Leiden (FVL), prothrombin gene mutation, methylenetetrahydrofolate reductase enzyme (MTHFR) C677T, MTHFR A1298C, and plasminogen activator inhibitor-1 (PAI-1), alongside the assessment of protein C (PC), protein S (PS), and antithrombin (AT) levels. The study analyzed the association between inherited thrombophilic polymorphisms and pregnancy complications linked to placental insufficiency, such as gestational hypertension (GH), preeclampsia (PE), intrauterine death (IUD), fetal growth restriction (FGR), and placental abruption. Results: The prevalence of identifiable thrombophilic polymorphism mutations was 61.9% (95% confidence interval - CI 52.4–70.8%), with the most common single mutation being PAI-1 4G/5G (12/105, 11.4%, 95% CI 6.4–18.5). The most frequent combined mutation was heterozygosity for MTHFR C677T and PAI-1 (12/105, 11.4%, 95% CI 6.4–18.5). Notably, no FVL homozygous carriers or single homozygous and heterozygous carriers for prothrombin polymorphisms were found. Additionally, no deficiencies in PC and AT were detected among participants. Except for homozygosity for PAI-1, none of the studied polymorphisms demonstrated a significant association with pregnancy complications linked to placental insufficiency. Conclusions: The asymptomatic carriers of inherited thrombophilic polymorphisms do not have an increased risk of adverse perinatal outcomes.

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Section: Discussionmentioning

confidence: 99%

Impact of Thrombophilic Polymorphisms in Antenatal Women on Perinatal Health: A Single-Center Prospective Study

Sokol Karadjole,

D’Amato,

Milošević

et al. 2024

JPM

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“…However, data on the discovered FI variants and their prognostic and therapeutic implications are missing [67]. A recently published systematic review and meta-analysis study on thrombophilic gene polymorphisms and RPL suggests that they may be used as effective clinical indicators to assess RPL risks or to assist unexplained RPL women uncover plausible factors, as well as to allow for focused treatment [50]. One of the published meta-analyses on 99 genetic analysis studies of the C677T variant in the MTHFR gene in venous thrombosis confirmed the contribution toward the development of pulmonary embolism [68].…”

Section: Discussionmentioning

confidence: 99%

“…Hereditary thrombophilia is considered a risk factor in reproductive disorders [49]. However, in RPL [50], and then in cases of IVF [51], limited studies have been documented that have tried to connect infertility in women and genetic variants of thrombophilia [52,53]. A couple of studies have been documented in the Saudi population that were focused on recurrent miscarriage [54] that also included healthy subjects [55], and both of these studies showed positive associations.…”

Section: Introductionmentioning

confidence: 99%

Molecular Screening of the Thrombophilic Variants Performed at G-141 Laboratory among Saudi Infertile Women

Alageel,

Alhaizan,

Neyazi

et al. 2023

Applied Sciences

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Infertility is a major issue at present and is a common disease that exists in both male and female reproductive systems, described as failure to attain pregnancy. The most important physiological phenomenon for establishing clinical pharmacy is defined as female infertility (FI). Obesity enhances the risks for many chronic disorders, especially causing a high risk for women’s reproductive health. The relationship between infertile women and thrombophilia is characterized by abnormal blood coagulation. Among the thrombophilic variants, Factor V Leiden (FVL), prothrombin (PT) and methyl tetrahydrofolate reductase (MTHFR) in genes such as G1691A (rs6020), G20210A (rs1799963) and C677T (rs1801133) are commonly studied in the majority of human diseases. In this case–control study, we investigated the role of thrombophilic variants such as G1691A, G20210A and C677T in the FVL, PII and MTHFR genes in Saudi infertile women. Based on sample size calculation, 100 female infertile and 100 control (fertile) women were selected based on inclusion and exclusion criteria. Genotyping was performed with polymerase chain reaction and followed with precise restriction enzymes, which can accurately detect the nucleotide amendment variants in G1691A, G20210A and C677T. The required statistics were applied between the case (infertile) and control (fertile) women to document the role of the G1691A, G20210A and C677T variants in Saudi infertile women. In this study, age, weight and BMI were found to be high in the control women in comparison to the infertile women. None of the genotypes, genetic models or allele frequencies were associated with G1691A, G20210A or C677T SNPs (p > 0.05). Furthermore, the regression model and ANOVA analysis also showed negative statistical associations. The combination of genotypes and allele frequencies among G1691A, G20210A and C677T SNPs showed positive associations in the recessive model (p = 0.0006). Finally, the GMDR model showed moderate associations with the gene–gene interaction, dendrogram and depletion models. Finally, this study confirmed that thrombophilic SNPs have no role and may not be involved in Saudi infertile women.

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The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight

Hoirisch-Clapauch

2024

Semin Thromb Hemost

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Fibrinolytic enzymes modify various substrates required for tissue remodeling, playing a crucial role in mechanisms underlying resilience, reward processing, ovulation, embryo implantation, and placentation. Individuals with low resilience and reduced reward responsiveness, when exposed to chronic stress, are at increased risk of experiencing a range of negative emotions. Chronic anxiety and melancholia are examples of negative emotions associated with hypercortisolism, while fear and atypical depression are characterized by systemic inflammation. Both cortisol and inflammatory cytokines stimulate the production of plasminogen activator inhibitor-1 (PAI-1), a potent fibrinolysis inhibitor. Chronic anxiety, fear, and depression are among the many hypofibrinolytic conditions increasing the risk of oligo-anovulation, miscarriage, fetal growth restriction, and preeclampsia. Although significant, the impact of negative emotions on implantation is not as obvious as on ovulation or placentation. Other hypofibrinolytic conditions that may affect female reproduction through mechanisms dependent or independent of PAI-1 include metabolic disturbances (e.g., due to consumption of highly palatable foods, often used to alleviate negative affect), inflammation, hyperhomocysteinemia, hypothyroidism, hypercortisolism, antiphospholipid antibodies, and the 4G allele of the PAI-1 gene. Benzodiazepines and antidepressants should be used with caution in the first trimester as this combination may cause malformations. Also, selective serotonin reuptake inhibitors have fibrinolytic properties that increase the risk of bleeding after surgical procedures. Psychological interventions, especially group therapy, are effective in the prevention of reproductive disorders. Controlled trials are needed to test the hypothesis that female reproductive health depends on psychological well-being, a balanced diet and physical activity, suppression of inflammation and autoantibodies, and homocysteine and hormonal homeostasis.

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Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis

Cited by 6 publications

References 136 publications

Impact of Thrombophilic Polymorphisms in Antenatal Women on Perinatal Health: A Single-Center Prospective Study

Impact of Thrombophilic Polymorphisms in Antenatal Women on Perinatal Health: A Single-Center Prospective Study

Molecular Screening of the Thrombophilic Variants Performed at G-141 Laboratory among Saudi Infertile Women

The Impact of Emotional Responses on Female Reproduction: Fibrinolysis in the Spotlight

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