*3 or more consecutive pregnancies ending
spontaneously before fetal viability.
*2 or more because recurrent risks & subsequent
outcomes are similar for women having 2 or 3 prior
losses (Hill,1994)
Recurrent early pregnancy loss: 30 yr.).
RPL rate is 50% in those 40 yrs or older
(Clifford et al,1997)
1st trimester losses account for 75% of RPL
2nd trimester losses the remaining 25%
Can be established in only 30% (Trout et
al,2000 to 50% (ACOG,2001)
Different from causes of single sporadic
abortion
..Persistent & proved each time
..Some diseases cause sporadic but not
repeated abortion
..The contribution is different
Causes
•Possible
•Doubtful
•Unexplained: 50% (ACOG,2001)
to 70% (Trout et al,2000)
I. Genetic: 25%
II. Anatomic:(10%) 1. Congenital uterine malformation.
2. Submucous fibroid
3. Cervical incompetence
4. Severe IU synechiae
III. Endocrine: (5%) 1.Uncontrolled DM
2. Uncontrolled thyroid disease
3. PCOS
IV. Autoimmune (10%).
V. Alcohol & smoking
Incidence:
25% of RPL* (Edmonds& Bennet,1987).
60% of sporadic miscarriage
*70% of first trimester,
30% of 2nd trimester.
Chromosomal fetal anomalies: 25%
Different from those in single spontaneous
abortion: Aneuploidy: Trisomy: 50% due to
nondisjunction or translocation, Monosomy:
25%, Triploidy: 15%, Tetraploidy: 5%,
Structural anomaly: 3%
Chromosomal anomalies in the parents: 5%
suggesting that the fetal abnormality is not
secondary to a parental problem.
Most frequently balanced translocation
Effect of aging of the ovum or
sperm: >2 days: increased
chromosomal abnormalities
(aneuploidy)
Recurrence: Most occur as non-recurrent
chance phenomenon, but if first abortion
was chromosomally abnormal: increased
risk of chromosomal abnormalities in
subsequent pregnancies
Diagnosis:
1. Peripheral blood
Karyotyping of the parents in all
couples with RPL.
2. Karyotyping of the abortus
(fetal/placental chromosome)
Treatment: No treatment
Gamete donation
Genetic counseling to alleviate stress
If aneuplody is documented: accurately
timed insemination as aneuploidy is
due to aging of ovum & sperm
If euploidy: Look for other causes
Why Karyotype of the parents?
1. Couples would like to know the cause
2. A couple in which one partner carries a
balanced chromosome abnormality is at
increased risk for having:
a. Fetus with an unbalanced chromosome
abnormality & may benefit from prenatal
genetic diagnosis.
b. Offspring carrying the same abnormality
1. Congenital anomalies of the uterus
Incidence:
10 % of RPL
Types:
1. Septate uterus: is the most frequent
abnormality associated with RPL.
Incidence of uterine septum in women with a history of RA is similar to that identified in
women with reproductive histories (Simon et al,1991). Septate or bicornuate uteri
are unlikely to cause RPL (Balen,1999)
2. Bicornuate, didelphic, .unicornuate, DES uterus
Mechanism:
Impaired vascularization of pregnancy & limited
space for the fetus. However the vascular density of
uterine septa is similar to that of the normal uterine
wall (Dabiarashrafi et al,1995)
Diagnosis:
1. TVS
2. Sonohysterography
3. 3D US
4. HSG: as a routine is questionable since it is associated
with patient discomfort, risk of pelvic infection, relatively
inaccurate & offers the same diagnostic sensitivity as TVS
(Cliford et al,1994).
5. Hysteroscopy
6. MRI
Treatment:
Hysteroscopic division of the septum;
reduction of miscarriage rate from 85% to
10% (Daiter,2001)
Prophylactic cerclage has not been
supported from RC study (Lazar et al, 1984).
However when nothing else to offer , cervical cerclage is
worthwhile ; e.g. in patients with late losses & mullerian
anomalies e.g bicornuate uterus or unicornuate uterus
2. Cervical incompetence
May cause 2nd trimester abortion.
It is thought to be over-diagnosed because there is no
reliable diagnostic tests & the diagnosis is most
commonly based on characteristic history.
Cervical cerclage should only be considered when the
history of miscarriage is preceded by spontaneous
rupture of membranes or painless cervical dilatation.
The MRC/RCOG trial of the use of cervical cerclage
reported a small decrease in PTL, but no significant
improvement in fetal survival (1993) (B)
3. Submucous Fibroid
Hysteroscopic removal of
submucous fibroid
4.Severe Intrautrine synechiae
Hysteroscopic treatment of severe
IU synechiae
1. D.M. & thyroid disease
Well controlled D.M. is not a risk factor for
RPL, nor treated thyroid dysfunction.
Routine screening for occult D.M &
thyroid disease should not be performed
in asymptomatic women with RPL.(C).
The high frequency of hypothyroidism warrants
screening of TSH (Plouffe et al,1992).
2. PCOS
36-56% of RPL have PCOS (Clifford et
al,1994; Liddell et al,1997)
•Hypersecretion of LH is not a cause of
RPL (Balen,1999, Rai et al,2000)
Suppression of LH secretion with GnRh
agonist prior to ovulation induction yielded
no difference in outcome (Clifford et
al,1996) (A).
•Oligomenorrhea was 10 times
more important than any other risk
factors in predicting RPL (Quenby
et al,1993).
•Women with PCOS who miscarry
have higher levels of androgens
(Tulppala et al,1993)
•Women with RPL have a significantly increased
prevalence of insulin resistance when compared to
matched fertile control (Barker et al,2001).
•Fasting glucose /insulin ratio is recommended in
PCOS with RPL.
•Metformin has been continued during pregnancy to
prevent RPL (Jakubowiciz et al,2000; Gluek et al,
2001)
•No known therapy for reducing the risk of pregnancy
loss in women with PCOS (ACOG,2001)
Self Ag. = humoral or cellular response is directed
against a specific component of the host.
Antiphospholipid Ab (aPL): Lupus anticoagulant
(LA), anticardiolipin (aCL). Other aPl are of no
clinical value (C ) (Branch et al,1997)
Mechanism: Abs are directed against platelets &
vascular endothelium
vascular damage, thrombosis & placental infarction
abortion, fetal morbidity & death.
Incidence: 10% of RPL
Screening: activated partial thromplastin time:
prolonged
Diagnosis: 2 positive tests at least 6 w apart because of
the inter-laboratory variation
{ 1. Temporal fluctuation in individual patients 2. Transient
positivety secondary to viral & other infections 3. Suboptimal
sample collection & preparation. 4. Lack of standardization of
laboratory tests}
Definite APS is diagnosed when AB levels are
repeatedly >20 units & levels 10 mIU/ml or
E2 >50 pg/ml
Incidence: 58% of unexplained RPL
(Trout et al,2000)
4. Thyriod autoantibodies
Are associated with increased rate of RPL
if identified in early pregnancy or
immediately before pregnancy (Stagnaro et
al,1990)
Rushworth et al (2000):thyroid
autoantibodies is not indicated for
investigation of unexplained RPL
Treatment: IV immunoglobulin.
Prediction of further abortion in
patients with a historyof
unexplained RPL
A shortened aPTT before conception
is associated with further abortion in
patients with a history of
unexplained RPL (Ogasawara et al,
1998)
Treatment
1. Reassurance: attendance at a
dedicated early pregnancy assessment
clinic. Informative & sympathetic
counseling.
Success: 35-85%
2. Empirical therapy is unnecessary
(ACOG,2001)
a. Low dose aspirin did not improve pregnancy
outcome in unexplained RPL (Tulppala et al,1997)
Low dose aspirin is beneficial in treating second
trimester unexplained RPL, but not beneficial in
treating first trimester unexplained RPL(Rai et
al,2000)
b. HCG: Insufficient evidence to support use of HCG
in unexplained RPL (Cochrane libarary, 2002)
c. Immunotherapy of no benefit in unexplained RPL
(Chocrane libarary,2002)
1. Karyotyping of the peripheral
blood of parents & of the abortus
2. Pelvic US to assess ovarian
morphology & the uterine cavity.
3. LA & aCL
1. Cultures for bacteria, virus
2. GTT, Thyroid tests
3. Other aPL AB other than aCL & AC
4. Antinuclear antibodies
5. Antithyroid antibodies
6. Tests of thrombophelia
7. Parental human leukocyte antigen (HLA)
8. Maternal antipaternal antibodies
1. Karyotyping abnormalities: clinical
geneticist.
2. Positive APA: low dose aspirin & low
dose heparin.
3. Uterine septum, submucous fibroid,
severe IU adhesions: hysteroscopic
evaluation & surgery
4. Unexplained: Reassurance
1.Leukocyte immunization
2.Intravenous immunoglobulin
3.Luteal phase support with
progesterone
Benha University Hospital, EGYPT
E-mail: elnashar53@hotmail.com