الفهرس 
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Abstract
Recurrent pregnancy loss is considered as a major devastating obstetric and gynecological health problem. Many clinicians define RPL as three or more consecutive pregnancies ending spontaneously before the 20th week of gestation; however, two or more pregnancy losses, including those which are not consecutive, are also recently considered as recurrent spontaneous abortions.
According to the first definition, RPL occurs in about 1% of all couples. However, this frequency increases up to 5% when it is defined as two or more losses.
There are many known risk factors and causes of RPL including parental chromosomal abnormalities, APAS, and a subset of uterine abnormalities. Other suspected but not proven causes as alloimmunity, endocrinopathies, environmental toxins, inherited thrombophilias and various infections. However, still up to 40–50% of cases are considered unexplained.
Thrombophilia refers to any persistent identifiable hypercoagulable state either acquired or inherited, associated with an increased risk of both venous and arterial thromboembolism. The most important form of acquired thrombophilia is APAS which has well established role in the incidence of RPL.
Inherited thrombophilias include a group of mostly autosomal dominant, inherited gene mutations leading to hypercoagulable state, including ATIII deficiency, protein C and protein S deficiencies, and mutations in the genes encoding clotting factors as Prothrombin gene mutation (G20210A), FVL and others. They are one of the most important predisposing factors for VTE in pregnancy and many studies suggested their role in many adverse pregnancy outcomes as RPL.
FVL is the most common known inherited thrombophilia. It is an autosomal dominant genetic condition, which occurs as a result of a single point mutation in the factor V gene. This mutation results in a replacement of Arginine (R) 506 with Glutamine (Q) in one of the factor V cleavage sites for APC (Arg 506) where APC acts. This substitution leads to a factor V species that cannot be degraded by APC. The rate of inactivation of FVL by APC is 10-20 fold lower compared to the rate of degradation of normal factor V, explaining the hyper-coagulable state and the life – long increase risk of thrombosis.
Recently, the FVL mutation was identified as the most common genetic predisposition to thrombosis. Over the past 3 decades, many studies have suggested the strong association between FVL and many adverse pregnancy outcomes as preeclampsia, IUGR, placental abruption and RPL. However many studies have refuted this. Because of the heterogeneity of these results, the ACOG (2013) has concluded that a definitive causal link cannot be made between inherited thrombophilias and adverse pregnancy outcomes.
The aim of this case control study was to investigate the role of FVL mutation in RPL. We compared the prevalence of FVL among 83 patients with history of 3 or more first trimesteric pregnancy losses (the case group) with an equal number of women with no history of RPL (the control group), after exclusion of the most common known causes for RPL as APAS, anatomical intrauterine abnormalities (as assessed by 3D ultrasound) and other identifiable causes of RPL as diabetes, thyroid disease…
After fulfilling the inclusion and exclusion criteria, APC resistance test, the screening test for FVL, was done for each woman of both groups. It is calculated by normalized ratio (n-APC-SR( ,which is obtain by (APTT values obtained from a patient plasma with and without adding APC, then compared with the corresponding APTT values of a reference plasma). Patients with APCR usually have a normalized ratio of <0.82 compared with a ratio of >0.82 for women without APCR.
Our results revealed the following:
● No statistically significant differences between both groups as regards age.
● Statistically significant differences were found as regards number of successful pregnancies and number of abortions with no statistically difference regarding gestational age at abortion.
● Abnormal APCR test values were found in a total of 22 cases in our study, 7 cases in the control group (8%) and 15 in the case group (18%) with no statistically significant differences.
● No statistically significant differences were found between both groups as regards APCR test values.
So, Results showed that there is increased incidence of RPL in patients with FVL however with no statistically significant results.
We concluded in this study, that isolated FVL may increase the risk of RPL, however it is unlikely to be an important cause as no statistically significant difference is found between the case and control groups.
Further larger retrospective and prospective studies are needed to determine the prevalence of FVL and its role in RPL and other adverse pregnancy outcomes in the Middle East and particularly Egypt. These studies should include DNA studying for diagnosis of homozygotes and heterozygotes and should include also other inherited thrombophilia