Download Pregnancy Loss

6102-6102 ‫المرحلة الخامسة‬
Recurrent Miscarriage
‫د شذى سامي‬
FICOG
Objectives
Define the recurrent miscarriage
Causes of misscarge
Modality of treatment
prognosis
 Loss of three or more consecutive pregnancies at <20 weeks
gestation (excluding ectopic, molar and bio chemical pregnancies)
Classify to two subgroups:
 Primary: Without prior live birth
secondary RM with prior live birth
Incidence:
 1 – 2% will experience three consecutive losses
 But thereafter the chance of successful livebirth is ≈ 40%
Factors Associated with Miscarriage
6102-6102 ‫المرحلة الخامسة‬
 Maternal age
 (Paternal age)
 Alcohol abuse
 Smoking
 Excessive caffeine consumption
 Maternal obesity
 Anaesthetic gases – data incomplete
Possible Causes of Recurrent Miscarriage
 Antiphospholipid Syndrome
 Parental Chromosome Rearrangement
 Uterine Abnormalities
 Cervical Incompetence
 Endocrine abnormalities in the mother
 Infective agents
 Immune factors
 Inherited Thrombophilias
 Idiopathic/Unknown
>50%
1.GENETIC FACTORS
6102-6102 ‫المرحلة الخامسة‬
The highest rate of cytogenetically abnormal fetuses occurs earliest in
gestation, with rates declining after the embryonic period (>30 mm
crown–rump length (CRL)).
a.Parental chromosomal abnormalities
In approximately 3–5% of couples with RPL, one of the partners carries
a balanced structural chromosomal anomaly , the most common being
balanced reciprocal (60%) and Robert- sonian (40%) translocations.
b.Aneuploidy
The risk of aneuploidy (meiotic non-disjunction, polypoid from
fertilization abnormalities) increases as the number of previous miscarriages increases.
2.ANATOMIC CAUSES
Acquired and congenital uterine abnormalities are responsible for 10–
15% of RPL and may be associated with fetal growth restriction and
preterm delivery.
Uterine anomalies
The most frequent uterine defects include septate, bicornuate and
didelphic abnormalities. The septate uterus is most common and associated with the poorest reproductive outcome (miscarriage rate more
than 60% in untreated cases) Other anatomic causes of RPL are
diethylstilbestrol exposure related anomalies, Asherman’s syndrome,
6102-6102 ‫المرحلة الخامسة‬
leiomyomas and endometrial polyps. A primary endometrial receptor
defect appears to be responsible for RPL in some patients
3.Cervical incompetence
No satisfactory objective test is available for cervical incompetence, and
diagnosis is usually made on the basis of a history of late miscarriages,
preceded by spontaneous rupture of membranes and painless cervical
dilatation.
4.Immune mechanism
Both autoimmune and alloimmune mechanisms have been proposed as
explanations for RPL.
Antiphospholipid syndrome
Antiphospholipid antibodies (aPL) are present in 15% of women with
RPL and 33% of women with systemic lupus erythematosus (SLE). In
women with RPL associated with untreated aPL, Primary
antiphospholipid syndrome (APS), which predominantly affects young
women, refers to the association of aPL and adverse pregnancy outcome
or vascular thrombosis. Adverse pregnancy outcomes include three or
more consecutive miscarriages before 10 weeks’ gestation; one or more
morphologically normal fetal loss after 10 weeks’ gestation; and one or
more preterm birth before 34th week of gestation due to severe preeclampsia, eclampsia or placental insufficiency. When APS exists in
chronic inflammatory disorders, such as SLE, it is referred to as
secondary APS.
Characteristic fatures:
6102-6102 ‫المرحلة الخامسة‬
clinically : APS presents in two major ways:
1-thrombosis (venous or
arterial)
2-pregnancy loss.
Thrombocytopenia, present in about 20% of cases, canbe an
important clue.
laboratory : persistently elevated levels of antibodies directed against
membrane anionic phospholipids (ie, anticardiolipin [aCL] antibody,
antiphosphatidylserine) or their associated plasma proteins,
predominantly beta-2 glycoprotein I (apolipoprotein H); or evidence of a
circulating anticoagulant
Laboratory criteria
Patients must have
(1) medium to high levels of immunoglobulin G (IgG) or
immunoglobulin M (IgM) anticardiolipin (aCL),
(2) anti–beta-2 glycoprotein I,
or (3) LA on at least 2 occasions at least 12 weeks apart
Pregnancy morbidity
6102-6102 ‫المرحلة الخامسة‬
One or more late-term (>10 weeks' gestation) spontaneous
abortions
One or more premature births of a morphologically healthy
neonate at or before 34 weeks’ gestation because of severe
preeclampsia or eclampsia or severe placental insufficiency
Three or more unexplained, consecutive, spontaneous abortions
before 10 weeks’ gestation
Treatment
 Asymptomatic Antiphospholipid Antibodies
Patients with aPL but no history of thrombosis or pregnancy loss
1- should avoid medications that might contribute to
hypercoagulability, including oral contraceptives and hormone therapy
2-. Other risk factors for hypercoagulability should be minimized.
3- Low dose aspirin can be considered as a prophylactic therapy, but
efficacy has not been proven in clinical trials.
4- hydroxychloroquine can be considered as a possible prophylactic
intervention in SLE patients
 Pregnancy Loss
For it ‘s prevention prophylactic doses of unfractionated or lowmolecularweight heparin plus low dose aspirin (81 mg)
This regimen causes less maternal and pregnancy morbidity than the
older regimens of prednisone and aspirin.
6102-6102 ‫المرحلة الخامسة‬
Unfortunately, the heparin and aspirin regimen is successful in only 75%
of pregnancies.
If unsuccessful, there is some scientific rationale to
the addition of intravenous immunoglobulin in the next
pregnancy.
Thrombosis :
 The treatment of an acute thrombotic event (thrombolysis and/or
heparin) .
 Because of the high risk of recurrence of thrombosis in APS, a
strong case can be made for life-long anticoagulation after a first
thrombotic event.
If anticoagulation is stopped after 6 months,there is a recurrence rate of
20% or more .
 The APS patient with thrombosis and thrombocytopenia
is of special concern.
 Thrombocytopenia does not protect the APS patient from
thrombosis.
 Most thrombocytopenia in APS is mild, in the range of 90 to
140,000.
 Profound thrombocytopenia, however, would greatly
increase the risk of bleeding with anticoagulation.
 The platelet count should be stable at above 50,000 before
6102-6102 ‫المرحلة الخامسة‬
chronic anticoagulation is begun, and the INR goal
would be 2.0 in such a patient
5.THROMBOPHILIAS AND FIBRINOLYTIC FACTORS
a presumed mechanism being defective placentation and microthrombi
in the placental vasculature. Inherited thrombophilias include factor V
Leiden, protein C and S deficiency, antithrombin III deficiency,
activated prothrombin C resistance (APCR),. Acquired thrombophilia
includes anticardiolipin antibodies and lupus anticoagulant. In the
absence of treatment, factor V Leiden is associated with an increased
risk of miscarriage, compared with a normal factor V genotype. Factor V
Leiden is carried by 5% of Caucasians, but is rarely found among
Blacks. Other inherited thrombophilias are rare, and no conclusive
studies have been conducted to prove their causality in RPL.
6.ENDOCRINE
Endocrine factors may be responsible for 15–20% of RPL.
a.Polycystic ovarian syndrome
Women with polycystic ovarian syndrome (PCOS) have a miscarriage
rate of 20–40% as compared to the general obstetric population (10–
6102-6102 ‫المرحلة الخامسة‬
20%). This may be related to elevated serum luteinizing hormone (LH)
levels, high testosterone and androstenedione concentrations, or insulin
resistance
b.Luteal phase defect
It is controversial as to whether such a defect exists and whether it is
related to miscarriage
c.Diabetes
Diabetic gravida with hemoglobin A1c levels in the first trimester of
more than 8 are at increased risk of miscarriage and fetal malformations.
e.Hyperprolactinemia
Normal circulating levels of prolactin may play an important role in
maintaining pregnancy.
f.Thyroid disease
Poorly controlled thyroid disease (hypo- or hyperthyroidism) is
associated with infertility and pregnancy loss. Excess thyroid hormone
increases the risk of miscarriage.
7.Infection
Some infections, including listeriosis, toxo- plasmosis, cytomegalovirus
and primary genital herpes, cause sporadic pregnancy loss, but no
infectious agent has been proven to cause RPL
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Investigations
1. peripheral blood karyotyping, and cytogenetic analysis of the
products of conception
2. Transvaginal ultrasound is useful for making a diagnosis of uterine
anomalies. Transvaginal ultrasound assessment of the cervix
during pregnancy may be useful in predicting preterm birth in
cases of suspected cervical weakness.
3. Hysteroscopy is usually reserved for patients in whom intrauterine
pathology is suspected and operative hysteroscopy is necessary.
4. . Magnetic resonance imaging (MRI) is use- ful for distinguishing
between a septate and bicornuate uterus
5. Transvaginal ultrasound assessment of the cervix during pregnancy
may be useful in predicting preterm birth in cases of suspected
cervical weakness.
6. To diagnose APS, it is mandatory that the patient have two positive
tests at least 6 weeksapart for either lupus anticoagulant or anticardiolipin antibodies (aCL) of IgG and/or IgM class
7. Thyroid function test
8. immunological testing This includes NK cells (number and
activation), HLA typing, mixed lymphocyte antibody tests and
mixed lymphocyte culture reactions
9. A full inherited and acquired thrombophilia screen is
recommended
10.
Blood sugar ,serum prolactin
11.
Screening for and treatment of bacterial vaginosis in early
pregnancy in women with a history of second trimester miscarriage
or pre- term labor may reduce the risk of RP
Treatment:
6102-6102 ‫المرحلة الخامسة‬
According to cause:
A.Genetic counseling can provide the couple with a prognosis for future
pregnancy, as well as offer familial chromosomal studies and
appropriate preimplantation genetic diagnos- tic procedures in future
pregnancies. In addi- tion, the couple should be informed that they have
a 40–50% chance of a healthy live birth in future untreated pregnancies
following natural conception
B. a combination therapy of low dose aspirin (75 mg) plus heparin (5000
U once or twice a day) for APL.
C. The general approach is to treat women with thrombophilia with a
combination of low dose aspirin and low molecular weight heparin.
Therapy may need to be started before pregnancy occurs and continued
to 6 weeks after birth
D.surgical correction of uterine anomly include
metroplasty.hystroscopic resction of endometrial polyp.fibroid….
E.Treatment with low dose prednisolone could be considered as a
treatment modality in patients who have raised ANA.
F. Diabetic women with RPL should be treated in a multidisciplinary
joint diabetic clinic
G. Treatment to lower prolactin concentrations was associ- ated with a
higher rate of successful pregnancy,treatment of thyroid disease
For unexplained RPL
Treatment include:
6102-6102 ‫المرحلة الخامسة‬
1. Lifestyle modification Weight loss, exer- cise, avoiding alcohol,
caffeine intake and smoking.
2. Progesterone Large randomized controlled studies demonstrating
the efficacy of pro- gesterone treatment are lacking, but the drug is
widely prescribed to women with RPL.
3.IVF and preimplantation genetic diagnosis (PGD)
4. Oocyte donation Ovum donation can over- come the problem of
poor quality oocytes
5. Dietary supplemen- tation with vitamin B complex, including folic
acid and co-enzyme Q10 may suggest a reduction in RPL.