DISCUSSION
Pregnancy loss (PL) is a common medical problem among reproductive-age
women. However, relatively few women having one pregnancy loss
experience multiple or recurrent pregnancy loss.(12)Maintaining a normal pregnancy requires a series of differential gene
expressions. FVL and MTHFR gene mutations are suggested as being reasons
for PL.(13) A study by Rodger et
al,(14) addressed the association of inherited
thrombophilia with PL in late primigravida, focusing on tests for FVL,
and MTHFR.(14) Associations between these heritable
thrombophilia variants and other serious pregnancy complications have
also been documented. The main underlying mechanisms seem to be
inhibition of trophoblast differentiation/invasion, and thrombosis of
the maternal side of the placenta resulting in placenta mediated
pregnancy complications and fetal loss.(15) However,
the relation between thrombophilia associated gene mutations and the
adverse obstetric outcome is controversial and data in the literature
are inconsistent because of study heterogeneity, potential publication
bias, and sequential testing.(16)
The present Cross-sectional study aimed to investigate the prevalence of
thrombophilic gene mutations (FVL and MTHFR C 667 T) with miscarriage in
primigravida in the late first trimester in an attempt to identify
candidates for anticoagulation to improve pregnancy outcome. This study
was conducted on 40 primigravida pregnant women with missed abortion in
the late first trimester. In the present study, the maternal age was
between 18.0 and 34.0years, with a mean of 24.23 ± 3.39 years. While the
gestational age was between 8.14 – 13.71 weeks with a mean of 10.91 ±
1.59 weeks. In our study, MTHFR C 667T mutations were present in 21
cases out of 40 participating cases (52.5%). Several
studies(17-19) reported increasing evidence for a
pathogenetic role of MTHFR gene polymorphism C677T in early PL. On the
other hand, other authors(20, 21) found a negative
association stating that MTHFR polymorphisms do not carry any risk in
pregnancy. The different inclusion criteria and the different ethnic
backgrounds of the selected patients may have contributed to the
contradictory results. According to FVL gene mutation, it was present in
12 cases out of 40 participating cases (30%). There is a large and
contradictory body of literature on the association between maternally
inherited thrombophilia and recurrent miscarriage(16,
22, 23). Although most(16, 24, 25) but not
all(26, 27) large prospective cohort studies have
failed to establish a consistent association between inherited
thrombophilia and early or late fetal loss. The case-control and
retrospective cohort studies have generally reported a link between FVL
heterozygosity and fetal loss after 10 weeks and particularly for
nonrecurrent loss after 20 weeks (28-31). This
suggests that any association is limited to high-risk populations and is
modest. Small case-control or retrospective cohort studies involving
heterogeneous populations have frequently reported contradictory
results, in part because of the influence of various confounders (e.g.
age, obesity) that are often not analyzed
appropriately.(29, 31)
In our study, there were 4 cases with combined thrombophilia (10 %).
Combined thrombophilia included FVL and MTHFR C677T only. The same
results were reported by previous
studies(17, 32-34) that identified combined
thrombophilic defects in women with recurrent PL, both early and late.
The study by Rozano-Gorelick et al,(32) reported that
combined thrombophilia exists when inherited and /or acquired
prothrombotic factors are pooled and every combination carries a
different risk of thrombosis. Furthermore, Sarig et
al,(26) proposed a scoring system for women with
thrombophilia based on four major categories: obstetric history,
previous thromboembolic events, family history of thrombosis or
gestational vascular complications, and type of thrombophilia. Combined
thrombophilia was given a high score and the total score is calculated
by summing up the scores of the four categories. Based upon the score
achieved, the pregnancy risk for an individual woman may be stratified
into four levels of risk: low ≤5, intermediate (score 6-10), high (score
11-14), and extremely high (score≥ 15). Finally, the number of
homozygous and heterozygous individuals were assessed for each of the
gene mutations studied. No homozygosity was detected in cases with FVL
gene mutation cases. However, 6 cases out of 21 cases of MTHFR gene
mutation were homozygous (15 %). A study by Couto et
al,(35) reported a low prevalence of homozygotes for
FVL and stated that the prothrombotic tendency during pregnancy and the
risk of thromboembolic events is increased with antithrombin deficiency
and homozygous FVL as single traits. In fact, the reported prevalence in
the general population of FVL homozygotes is less than 1% with a 2-4%
risk of venous thromboembolism (VTE) per pregnancy increasing to around
17% in women with a previous history of VTE.(36, 37)Hence, our study and other studies reported an association between some
types of thrombophilia and early miscarriage, but the absolute risk is
small and varies considerably among reports. However, most large
prospective cohort studies have failed to establish a consistent
association between inherited thrombophilias and adverse pregnancy
outcomes. According to recent evidence, screening for inherited
thrombophilia in women with a history of recurrent or nonrecurrent fetal
loss, abruption, intrauterine growth restriction, or preeclampsia is not
recommended.(38) Moreover, there is mounting evidence
that the administration of prophylactic anticoagulation during pregnancy
for the prevention of placenta- mediated pregnancy complications does
not improve pregnancy outcome in affected
patients.(39)