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INTRODUCTION
Recurrent pregnancy loss (RPL) is always a traumatic experience for the patient,
and also the most difficult areas in reproductive medicine. According to the Royal
College of Obstetricians and Gynaecologists (RCOG) Green-top Guideline No. 7 In
2011, miscarriage is the spontaneous loss of a pregnancy before the fetus reaches 24
weeks gestation.3 World Health Organization (WHO) recommends that in developing
countries, where the gestational age is often difficult to determine, the loss of pregnancy
when the fetus weighs under 500g is used to determine miscarriage. 1 Ideally, a threshold
of three or more consecutive miscarriages should be used for epidemiological studies
while clinical evaluation may proceed following two first-trimester pregnancy losses.
RPL affects 0.5-1% of couples. 5 This figure turned out to be twice the incidence that may
occur by chance, thus showing that there is an abnormality that can occur. It has been
found that the factors that could cause RPL including cytogenetic factors, anatomical
factors, antiphosopholipid syndrome, thrombophilias, hormonal or metabolic disorders,
infectious, autoimmune, sperm quality and lifestyle issues. 1
Only little consensus exists on the investigation should be done to find the
etiology of RPL along with effective treatment, and only a few are evidence-based. 1 This
paper aims to discuss the definition, epidemiology, etiology, investigation and
management in RPL.
CHAPTER II
LITERARY REVIEW
2.1 Definition
For the purposes of determining whether evaluation for RPL is appropriate,
pregnancy is defined as a clinical pregnancy documented by ultrasonography or
histopathological examination. 2 Williams Obstetrics 23rd edition defines RPL as three or
more consecutive pregnancy losses at 20 weeks or less with fetal weight less than 500
grams.5 World Health Organization (WHO) recommends to developing countries where
the gestational age is often difficult to determine, the loss of pregnancy when the fetus
weighs under 500g was used to determine miscarriage.1 Controversy has existed on the
number of miscarriages required to define RPL.
2.2 Epidemiology
RPL affects 0.5-1% of couples attempting to have children.
Identified causes
The risk of miscarriage increases with younger gestational age, with the majority
occuring in the first trimester. The prevalence of miscarriage increases with increasing
maternal age, this occurs due to increased chromosomal abnormalities, possibly due to
decreased oocyte quality, and decreased uterine and ovarian function. Increased paternal
age is also a risk factor for miscarriage. The highest risk of miscarriage in couples where
women over 35 and men over 40 years. The patients obstetric history may also increase
the risk of miscarriage. Retrospective and prospective studies have shown that the risk of
recurrent miscarriage increases after each miscarriage. RPL usually occurs at the same
gestational age. 1
Tabel 1: Risk of miscarriage at specific gestational ages 1
Gestation
Before 6 weeks
6-10 weeks
After10 weeks
Consecutive pregnancies
First pregnancy
After 1 miscarriage
After 2 miscarriage
After 3 miscarriages
31-45
2.3 Etiology
It has been found that the factors that could cause RPL including cytogenetic
factors, anatomical factors, thrombophilic factors, antiphosopholipid syndrome,
immunologic factors, endocrine factors, environmentral factors, infection, male factors,
and unexplained RPL.
2.3.1
Cytogenetic Abnormalities
60% of miscarriage are associated with sporadic chromosomal anomalies,
especially trisomy partly related to age. In miscarriage with normal
karyotypes, multiple morphological abnormalities in the fetus were
diagnosed with transcervical embryoscopy. The risk of sporadic
miscarriage between 6-12 weeks of gestation in women less than 35 years
old is 9% -12%. This risk is increased in women over 35 years due to a
very significant increase of the incidence of trisomy pregnancy. In women
over 40 years, the risk of miscarriage sporadic reached 50%. Aneuploidy
risk at any age is lower in women with RPL compared experiencing
sporadic miscarriage.
2.3.2.2 Leiomyoma
The more important factor that plays a role in the
relationship between fibroids and fertility is more towards the
location rather than the size of the fibroids. The fibroids can
change the shape of the uterine cavity such as submucosal and
intramural fibroids with an intracavity component was found to
increase the risk of miscarriage. One study found that intramural
fibroids can decrease the implantation in each cycle. A metaanalysis showed a decrease in the pregnancy rate with in vitro
fertilization (IVF), also with women with intramural fibroids that
does not change the shape of the cavity. 1
Figure 1.2 Uterine fibroid locations
intra-uterine
adhesions
can
be
caused
genital
tuberculosis. 1
incompetence
may
cause
repeated
mid-trimester
miscarriage. 1
2.3.3 Thrombophilic factors
It is hypothesized that thrombophilic disorders can cause thrombosis of the
utero-placental vasculature (spiral arteries and intervillous space) due to an
increase in a hemostatic response. The subsequent impaired placental
perfusion may lead to RPL, fetal death, pre-eclampsia, intra-uterine growth
retardation (IUGR), and placental abruption. 1
Inherited thrombophilia is a genetic condition in which there is an
increased risk of venous thrombosis. The various types are:
weeks' gestation
More than one preterm births under 34 weeks' gestation
because
of
pre-eclampsia,
eclampsia
or
placental
insufficiency. 1
Figure 1.3 Antiphospholipid antibodies against the placenta
inflammatory
pathways
on
the
surface
of
the
syncytiotrophoblast. 2
2.3.5 Allo-immune factors
The Hypothesis that some cases of RPL may be due to the failure
of maternal allo-immune recognition of the pregnancy has never been
proven. There is also no evidence to support the hypothesis that HLA
incompatibility between couples may lead to RPL.1
2.3.5.1 HLA Incompatibility
The human conceptus is a semi-allograft and hence
antigenically foreign to the mother. Therefore the process of
implantation may include mechanisms to prevent allograft
rejection, but once the immunological tolerance becomes
imbalanced, RPL may occur. The human leucocyte antigen (HLAG) seemed to play a major role in immune suppression at the
maternal-fetal interface and placental angiogenesis. HLA-G is
mainly expressed in extravillous trophoblasts (EVTs) of decidual
tissue, and has suppressive effects on NK cells, CD4+ and CD8+ T
cells, B lymphocyctes and antigen presenting cells such as
macrophages and dendritic cells. This interaction was essential for
9
polymorphism
and
RPL
have
showed
10
11
and
meticulous.
complete
history
of
previous
14
Here
are
some
methods
to
investigate
the
occurrence of RPL :
Karyotiping
Karyotiping from the conseptionals products
Cytogenic analysis should be carried out on the products of
conception in all patients with RPL. Normal karyotype
usually
indicates
better
prognosis
for
the
next
Conception
should
be
noted
that
the
by
the
balance
on
the
fetus.
However,
anomalies,
further
investigations
may
be
modalities
are
sonohysterography,
during
the
examination
procedure.6
more
accurate
results
when
compared
to
hysterosalpingography.7
Hereditary Thrombophilia
Testing for hereditary thrombophilia in women with a
history
of
idiopathic
RPL
is
still
controversial.
No
Practuce
Bulletin
No.
124,
hereditary
decisions,
and
not
for
the
treatment
All
women
with
RPL
should
be
screened
for
of
thyroid
manifestations.
The
disease
American
or
with
Thyroid
the
clinical
Association
Measurement
of
serum
progesterone
also
19
2.5 1Management
Treatments for recurrent miscarriage is based on the etiology.
However, all couples must be treated sensitively , sympathetic , and
with the proper emotional support. The best practice is to refer the
couple to a specialist clinic.
2.5.1
Anatomical
Correction of septate defect in particular may have beneficial effects and should
be considered in woman with RPL. Clinical management with Asherman
syndrome or intrauterine synechiae, uterine fibroids, and uterine polyps remain
controversial, some data showed that surgical treatment did not reduces the risk of
20
age
14-16
incompetence.
Autoimmune
Women with persistent
weeks
lupus
in
the
case
anticoagulant,
of
cervical
anticardiolipin
antibodies and hereditary trombophilia can be treated with low dose aspirin (81 mg) and enoxaparin (40 mg subcutaneously),
2.5.3
2.5.4
2.5.5
Infections
Routine serological tests, cultures cervical and endometrial
biopsy to detect the presence of infection in women with a
history of RPL is not recommended. Evaluation should be
performed only on those who are clinically suffering from
cervicitis, chronic or recurrent bacterial vaginosis or complaints
2.5.6
of pelvic infection.
Unexplained etiology
21
Etiology
Anatomical15
Treatment
Transabdominal
Cervicoisthmus
Outcome
- 25% had two successful
Cerclage
treatment
for
second-
consecutive
pregnancies after TCC
- Fetal survival after this
22
trimester
miscarriage
and
previous
failed
Antiphospolipid
Syndrome16,17,18
Hormonal disorder
19,20
subcutaneously
Progesterone
supplementation 10 mg/day
between
0,7)
supllementation Diminished
until
the
fetal
entire restriction,
pregnancy
incidences
growth
preterm
Alloimmune
21,22
birth rates.
IVIg 500mg/kg/month until Live birth
rate
was
23,24
150-180 g
80 mg of aspirin daily plus - 54,5% gave birth to live
subcutaneous
nadroparin
infant
23
(2850 IU)
24
CHAPTER III
CONCULSION
RPL is spontaneous abortion that occurs three times or more in a row. This
situation is a problem that requires special attention. Etiology of RPL is cytogenetic
factors , anatomical , antiphosopholipid syndrome, thrombophilias , hormonal or
metabolic disorders , infectious , autoimmune , sperm quality and lifestyle issues .
Some proper handling and safe to overcome the incidence of RPL had been
discovered. Since a woman is diagnosed RPL, she should do some medical
examination to prevent the miscarriages and eventually gave birth to the fetus is
viable. Some tests that could be done including genetic examination, anatomy,
endocrinology and immunology factors. Generally the management of RPL is based
on the underlying etiology. Examination using ultrasound can help review the
development of the fetus in the uterus.
25
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