1.

Antiphospholipid
syndrome

It is also known as lupus anticoagulant

syndrome and Hugh syndrome

is a disorder of coagulation, which causes blood

clots (thrombosis) in both arteries and veins,
(thrombocytopenia), as well as pregnancyrelated complications such as miscarriage or
stillbirth, preterm delivery, or severe
preeclampsia
aPL are present in 15% of women with recurrent
miscarriages.
In future untreated pregnancies, women with APS
have miscarriage rate as high as 90%.
The majority of miscarriages occur in the first
half of pregnancy. After establishment of fetal
heart.

Characterizied by : presence of APL

antibodies, which are frequently linked to
pregnancy losses in the pre-embryonic
(<6 wk), embryonic (6-9 wk), and fetal
(10 wk gestation) time periods
Antibodies could be IgG, IgM, or IgA
Three classes of clinically significant APL
antibodies have been identified:
1.anticardiolipin (aCL)
2. lupus anticoagulant (LAC3.
3.anti-2glycoprotein I antibodies
Diagnosis of APS requires the presence of
at least 1 of the clinical criteria and at
least 1 of the laboratory criteria:

Clinical criteria
1.Vascular thrombosis
2.Pregnancy morbidity
1) 3 or more unexplained consecutive
miscarriages with anatomic, genetic, and
hormonal causes excluded
2) 1 or more unexplained death(s) of a
morphologically normal fetus at or after the
10 weeks' gestation
3) 1 or more premature birth(s) of a
morphologically normal neonate at or before
34 weeks' gestation, associated with severe
preeclampsia or severe placental
insufficiency

Laboratory criteria
1.aCL: Immunoglobulin G (IgG) and/or
immunoglobulin M (IgM) isotype is present in
medium or high titer on 2 or more occasions, 6 or
more weeks apart.
*aCL is detected by ELISA
2.Demonstration of a prolonged phospholipiddependent coagulation on screening tests (eg,
activated partial thromboplastin time, kaolin
clotting time, dilute Russell viper venom time, dilute
prothrombin time, Textarin time)
* For lupus anticoagulant , we use the dilute
Russells viper venom time (dRVVT) test, as it is
more sensitive and specific than aPTT
3.Failure to correct the prolonged screening
test result by mixing with normal platelet-poor
plasma
4.Shortening or correction of the prolonged

These antibodies can be demonstrated with :

1.enzyme-linked immunosorbent assay (ELISA)
or
2. a coagulation result positive for LAC
The presence of the antibodies alone in the
absence of other clinical symptoms does not
define the syndrome.
Patients with the combination of high APLA
titers and the IgG isotype have a prognosis
worse than those with the combination of low
titers and the IgM isotype. (Higher risk of
miscourege)
However, the type of APLA (aCL, LAC, or anti
beta-2 glycoprotein I) does not influence the

Pathogenesis..
Pregnancy failure has been ascribed MAINLY
to placental thrombosis and infarction, but
those findings are not universal nor
specific to all cases of APAS.
Other theories:
1. defective trophoblast invasion
2. of dicidua and endometrial cell
3. decidualization in early pregnancy.
4. Increased trophoblast apoptosis.
5. inhbition of prostacyclin release which is a
bronchodilator and a platelet aggregator;
thrombosis of uteroplacental vasculature

clinical features
The clinical features are presented
according to the systems affected:
neurological
cardiac
renal
endocrine
dermatological
haematological
obstetric
thrombotic

thrombotic
Venous:
DVTs - these may be recurrent. In women these may
appear to be triggered by the use of the oral
contraceptive pill
hepatic thrombosis - antiphospholipid syndrome is the
second most common cause of hepatic thrombosis
retinal vein thrombosis
renal vein thrombosis
major vein thrombosis may involve thoracic outlet
veins or the inferior vena cava
Arterial thrombosis may cause ischaemia of almost
any organ

treatment of antiphospholipid syndrome

during pregnancy
low-dose aspirin and low-molecular weight
heparin are now the treatment of choice for
women with antiphospholipid syndrome and
a history of miscarriage.
usually, self-administered low-molecular
weight is given if there is a past history of
thrombosis .
the use of this may reduce the loss by 54%.

 first-line treatment is low dose aspirin - 75-100

mg daily .
patients with APS who have had a documented
major thrombotic event require long-term
treatment with warfarin or coumarin
anticoagulation.

 In women with a history of recurrent risk

pregnancies Random controlled trials showed
the live birth rate is 40% of reccurent
miscarriages with APS treated with low-dose
Aspirin
The live birth rate is 70% when they are
treated with low-dose aspirin & low dose
heparin
No proven role of steroids

2.Uterine anatomical
abnormalities..
Such as:
Intrauterine adhesions.
Congenitally abnormal uterus;
mullerian tract abnormalities.
Fibroids.
Cervical incompetence.

How do these factors cause RM?

* They can interfere with implantation and the
available space.
* Prevalence ranges from 1.8-37.6 %, this
variability reflects the differences in the
criteria and techniques used for the diagnosis
of RM.

Investigations..
All women with RM should have a pelvic U/S
to assess uterine anatomy and morphology.
What about Hysterosalpingography,
Hysteroscopy and Laparoscopy?
-The use of them is questionable!, they are
associated with patient discomfort, carry a
risk of infection and radiation exposure and
are no more sensitive than the U/S.

1)Intrauterine adhesions
Open uterine surgeries: They are associated
with postoperative infertility and carries a
significant risk of adhesions, scar rupture
during pregnancy.
PID.
Endometritis.
Ashermans syndrome:
Management:
-Lysis of adhesions under hysteroscopy.

2)Asherman syndrome
Caused by destruction to large areas of
endometrium by curettage. It is believed that
there is Insufficient endometium for
implantation.
Amenorrhea and recurrent abortion
Dx..HSG, best by hysteroscopy.
Tx.. Lysis by hysteroscopy and IUCD to
prevent recurrence.

3)Congenitally abnormal uterus.

Incidence less than 5% in RM.

*Uterine mllerian anomalies

Include :
1.septate
2. Unicornuate
3. Bicornuate
4.Didelphic uteri

Unicornuate uterus is least common,

but can result in malpresentation and
fetal growth restriction
The highest rate of reproductive
losses are found in bicornuate uteri
(47%)
Unicornuate uteri is (17%)
Uterine Septa have a (26%) risk of
reproductive loss.
All are frequently associated with
second trimester loss and preterm
delivery

1.Septate uterus
Failure of resorption of the septum between 2
uterine horns (could be partial or complete).
Mainly, they are associated with second
trimester miscarriages.
Vaginal hysteroscopy is best used for
treatment.

2.Bicornuate uterus
Commonly referred to as a "heart-shaped"
uterus, is a type of an uterine
malformation where two "horns" form at
the upper part of the uterus. non fusion of
mullarian ducts.
Effects on reproduction ;
1. Recurrent pregnancy loss
2. Preterm uterus
3. Malpresentation

Continue
Diagnosis
It is very difficult to diagnose a bicornuate
uterus using an ultrasound. Imaging
detection methods include:
hysterosalpingography and hysteroscopy.
MRI is emerging as an accurate detection
method
Treatment
some patients are candidates for surgery,
metroplasty.

Which type of fibroids mostly

associated with RM?

4)Fibroids
Mainly the sub-mucosal fibroid.
How do fibroids cause RM?
-Thinning of the endometrium over the
fibroid.
-Rapid growth caused by the hormones of
pregnancy.
-Lack of space of developing fetus.

-Management:
Surgical intervention.

5)Cervical weakness..
Loss of anatomical and physiological integrity
of cervix
Main cause of second trimester miscarriages.
10%

Causes..
Congenital
Obstetrics:
- difficult labor
- instrumental delivery
- traumatic delivery
- macrosomic baby
- Prolonged labor

When do we suspect cervical weakness

as a cause of RM?
History of late (2nd trimester) miscarriage,
preceded by spontaneous rupture of
membranes or painless cervical dilatation.
Painless abortion and no bleeding.
Its very difficult to identify women with cervical
weakness in the non-pregnant state, however,
transvaginal U/S assessment of the cervix
during pregnancy may be useful in predicting
preterm birth in some cases of suspected
cervical weakness.
Funnel shape cervix

Management:
Transvaginal cerclage (McDonald stitch) or
Transabdominal cerclage
TVC is usually performed after the 12th
week of gestation (13-19).
TAC is done at 10th week with subsequent
elective C/S, if TVC failed.

3.ENDOCRINE CAUSES
1-Diabetes
2-Thyroid diseases
3-Polycystic Ovary Syndrome
4-Luteal phase defect
5-Progesterone deficiency
6-Hyper-secretion of LH
7-Hyper-prolactinemia
8-Hyper-androgenemia
9-Oligo-menorrhea

1-Diabetes mellitus
Spontaneous abortion and major congenital
malformations are both increased in women with
insulin dependent diabetes
Poorly controlled diabetes increases the risk
of miscarriage by 2-3 fold in these women
compared with the general population
Women with diabetes can improve pregnancy
outcomes if
blood sugars are controlled before conception
Diabetic patients with good diabetic control have
the same risk for miscarrige as non diabetec
Early screaning for DM in women with risk factors

2-Thyriod diseases
There is evidence that thyroid disease can
cause miscarriage.
Screening is by Thyroid function test.
Mostly patients with thyriod disease induced
miscarriage are asymptomatic and diagnosed
by TFT
The presence of antithyriod anti bodies may
represent a generalized autoimmune
abnormality rather than a specific dysfuction

3-Poly cystic ovary

syndrome

Poly cystic ovary syndrome

A constellation of anovulation, oligomenorrhea or
amenorrhea, hirstutism, acne, male pattern
baldness, obesity and enlarged polycystic ovaries.
Diagnosis depends on abnormal hormonal assay,
increased LH:FSH and US findings.
It has been thought that hypersecretion of LH is the
cause of pregnancy loss
Attention is now focused on the relation b/n PCOS, insulin
resistance and RM.
Insulin resistance has been reported to be associated with
a higher rate of miscarriage among women of PCOS
compared to those non insulin resistance.

Poly cystic ovary syndrome

Recent studies report that using insulin
sensitizing agent as metformin
reduces hyperinsulinemia, reverse
the endocrinopathy and normalize
reproductive function.
Treatment targets the symptoms and
fertilty problems, ovulation
induction and IVF and other options.

4-Luteal phase defect

LPD is a defective corpus luteum with
insufficient progestrone production leading
to inadequate endometrial maturation.
Reported to be present in about 23-60% of
RM cases.
It could be assessed by detection of serum
progestrone level during the luteal
phase of the maternal cycle at day 21.
Also by endometrial biopsy to assess
the proliferative endometrium.

Luteal phase defect

Treatment is by progestrone or HCG
supplements.
Serum prog. Levels are not predictive
of pregnancy outcome, and no
evidence supports the use of
exogenous supplements early in
pregnancy to treat LPD and support
the pregnancy of RM patients

5-Hyperprolactinemia
Excess prolactin level lead to amenorrhea
and galactorrhea, in addition to
alterations in dopamine levels which
result in abnormal FSH and LH
secretions.
Can be caused by:
Primary hypothyroidism
Drugs..dopamine
antagonists,metaclopramides
Pituitary adenoma

Hyperprolactinemia
Although no single test can help determine the
etiology of hyperprolactinemia, a
prolactinoma is likely if the prolactin level is
greater than 250 ng/mL and less likely if
the level is less than 100 ng/mL
Correction with bromocriptene may lead to
higher live birth rate compared to non
corrected cases .

6-Oligomenorrhea
Represents 10% of RM
Associated with lower luteal phase estradiol
levels which may alter endometrial
receptivity with subsequent compromised
implantation and embryonic losses.
Associated wit higher chance of normal
karyotype miscarriage
in oligomenorrhea the use of HCG maybe of
benefit.