2020_2021 ‫المرحلة الخامسة‬

Recurrent Miscarriage
‫شذى سامي‬.‫د‬.‫م‬.‫أ‬

Objectives
At the end of this lecture the 5th year student will be able to:
1. Define the concept of “recurrent miscarriage”

2. Recognize the types of recurrent miscarriage.

3. List the causes of recurrent miscarriage.
4. Correlate the causes according to gestational age
5. Describe the modality of treatment.

Recurrent miscarriage: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

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 But thereafter the chance of successful livebirth is ≈ 40%

Risk factors for recurrent misscarriage

1. Epdimiological factors
1. Maternal age and number of previous miscarriage are two
independent risk factors
[Link] maternal age associated with decrease in both
number and quality of oocyte.
b. advanced paternal age the risk of miscarriage increased when
the age of man more than 40.
c. risk of further miscarriage was approximately 40% after three
consecutive pregnancy loss
[Link] and caffeine increased the risk in dose dependent
manner
[Link] increased both sporadic and recurrent miscarriage.
f. heavy alcoholic consumption is toxic to fetus its increased
risk sporadic misscraiage

2. Antiphospholipid syndrome
Antiphospholipid antibodies are present in 15% of women with
RPL, it’s the most treatable cause of recurrent [Link]
birth rate in recuurent miscarriage associated with
antiphospholipid syndrome without intervention is less
than10%
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Antiphospholipid syndrome refer to association between:
[Link] antibodies:lupus anticoagulant
,anticardiolipin and anti B2 glycoprotien -1 antibodies.

2. advanced pregnancy outcome or vascular thrombosis:

[Link] or more consecutive miscarriage before 10 weeks

b. one or more morphologically normal fetal loss after 10
weeks
c. one or more preterm births before 34 weeks due to placental
pathology.
The mechanism by which antiphospholipid syndrome cause
pregnancy morbidity include

■inhibtion of trophoblastic function and differentiation

■activation of complement pathway s result in local
inflammiation
■in later pregnancy thrombosis of uteroplacental vasculture.

[Link] FACTORS
This include:
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[Link] chromosomal rearrangements.
2-5% of couple with RM, one of partenars carry abalanced structural
chromosomal abnormality most commonly balancsd reciprocal or
robertsonian translocation.
[Link] chromosomal abnormality
Its account for30-57% of recurrent miscarriage, its increased with
increased of maternal age ,mainly anuoploidy

[Link] 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 asso-
ciated 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,
leiomyomas and endometrial polyps. A primary endometrial receptor
defect appears to be responsible for RPL in some patients

Cervical incompetence:
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More common cause of second trimester miscarriage,incidence un
known,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.

[Link] factors:
There is inssuffecient evidence to support the hypothesis of HLA
incompatablity between couples,the absence of maternal Leucocytotoxic
antibodies or the absence of maternal blocking antbodies.
6. Infection
The role of infection in RM is unclear,Any sever infection leads to
bactermia or viraemia can cause sporadic abortion.
Bacterial vaginosis in 1st trimester of pregnancy is arisk factor of 2nd
trimester and preterm delivery .

7. Inherted thrombophilia
Inhertd thrombophilia is apossible cause of RM and late pregnancy
complication fetal loss varies according to type of thrombophilia,
association between thrombophilia and late pregnancy loss is stronger
than with early pregnancy loss.
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[Link]
Endocrine factors may be responsible for 15–20% of RPL.
[Link] ovarian syndrome
Women with polycystic ovarian syndrome (PCOS) have a miscarriage
rate of 20–40% as compared to the general obstetric population (10–
20%). This may be related to elevated serum luteinizing hormone (LH)
levels, high testosterone and androstenedione concentrations, or insulin
resistance
[Link] phase defect
It is controversial as to whether such a defect exists and whether it is
related to miscarriage
[Link]
Diabetic gravida with hemoglobin A1c levels in the first trimester of
more than 8 are at increased risk of miscarriage and fetal malformations.
[Link]
Normal circulating levels of prolactin may play an important role in
maintaining pregnancy.
[Link] disease
Poorly controlled thyroid disease (hypo- or hyperthyroidism) is
associated with infertility and pregnancy loss. Excess thyroid hormone
increases the risk of miscarriage.
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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 useful 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 anti-
cardiolipin 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
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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:
According to cause:
[Link] counseling can provide the couple with a prognosis for future
pregnancy, as well as offer familial chromosomal studies and
appropriate preimplantation genetic diagnostic procedures in future
pregnancies. In addition, 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
[Link] correction of uterine anomly include
[Link] resction of endometrial [Link]….
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[Link] 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 associated with a
higher rate of successful pregnancy,treatment of thyroid disease

For unexplained RPL

Treatment include:
1. Lifestyle modification Weight loss, exercise, avoiding alcohol,
caffeine intake and smoking.
2. Progesterone Large randomized controlled studies demonstrating
the efficacy of progesterone treatment are lacking, but the drug is
widely prescribed to women with RPL.
[Link] and preimplantation genetic diagnosis (PGD)
4. Oocyte donation Ovum donation can overcome 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.