الفهرس 
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Abstract
Summary
ecurrent unexplained spontaneous miscarriage is
frustrating for patient and clinician which is defined as
loss of three or more consecutive pregnancies before 20 weeks’
gestation. Multiple etiologies for recurrent unexplained
spontaneous miscarriage have been reported including
autoimmune, endocrine, anatomic, genetic factors. However,
about 40%-50% of recurrent unexplained spontaneous
miscarriage are of unknown etiology and are classified as
URSM.
There is some suggestion that unexplained miscarriages
may be caused by an immune reaction as the fetus is secured
from the humoral immunity during normal pregnancy, cellmediated
immunity (cells and cytokines) was considered an
important etiologic factor in URSM. Previously, it was reported
that 37.1% of women with URSM have elevated peripheral
blood NK cells.
Treatment of URSM is a challenging issue. The
currently available lines of treatment according to simplicity of
use, reliability and degree of invasiveness include
corticosteroids as immunosuppressive drug and as miscarriages
are often associated with thrombosis aspirin and low molecular
weight heparin were used as the main treatment.
In pregnant women treatment with Sildenafil citrate
may improve blood flow to the placenta and fetus and is
R
Summary
128
currently being investigated as a treatment in fetal growth
restriction. Sildenafil citrate plays a major role in vascular
smooth muscle relaxation. Subsequently, it results in a
decrease in vascular resistance which leads to an increase in
uterine artery blood flow in early pregnancy, increase
endometrial thickness and also decrease cytotoxic uterine
Natural killer cells. The objective of this study was to assess
the efficacy of sildenafil therapy in prevention of recurrent
miscarriage.
The current study is a randomized controlled study
This study was conducted on 90 women recruited from Ain
Shams Maternity hospital after they had received information
on the purpose and course of the study from the medical
investigator and had provided the written consent. The 90
participants were divided into two equal groups using simple
random distribution technique, each group consists of 45
women, group A who received Sildenafil citrate and folic
acid, group B received placebo and folic acid.
Inclusion criteria: Age: 20-35 years., BMI (20-30), History
of three or more successive unexplained recurrent
miscarriage, Normal uterine cavity by hystrography or
hysteroscopy, No luteal phase defects by progesterone > 10
ng, Normal thyroid function (TSH, T3, T4), Normal lupus
anticoagulant measured by activated partial throbmoplastine
time (32-43 seconds), Normal anticardolipin (IgG < 20 gpl
Summary
129
and IgM < 15 MPL measured by ELISA),Normal anti
thyroid antibodies, Normal fasting 2hr postprandial blood
glucose test, normal antinuclear antibody, Normal parental
karyotyping.
Exclusion criteria: Age < 20 or>35 year, BMI<20
or>30,Systemic diseases that might affect pregnancy such as
diabetes or thyroid disorders or hypertension, History of
consanguinity, Family history of congenital anomaly, History
of autoimmune diseases, eg: systemic lupus, Congenital
anomaly in uterine cavity as bicornate or septate uterus,
Luteal phase defect and corpus luteum insufficiency, Uterine
masses as fibroid or polyps, Patient with patuoles os in the
previous pregnancies which are diagnosed sonographicaly or
by history of previous cercelage, patient with antiphosphlipid
syndrome, Cigarette smoking and alcohol.
The 90 participants were divided into two groups using
simple random distribution technique, group (A) received
Sildenafil citrate and folic acid while group (B) placebo
and folic acid.
Each patient was subjected to Detailed history taking
including:
- Personal: name, age, occupation, address and
relationship to the husband. Special habits of medical
Summary
130
importance as smoking, alcohol abuse, sleep, diet,
physical activity.
- Menstrual: age of menarche, regularity, duration,
painful or painless, amount of blood and LMP.
- Obstetric history: number of parity, gravidity, first and
second trimester history abortion, previous delivery
(term or preterm), previous pregnancy complications as:
ectopic, vesicular abortion, previous history of patulous
cervix by history of previous cercelage or by ultrasound
during previous pregnancies.
- Medical history: chronic diseases as hypertension,
diabetes, autoimmune disease and thyroid disorders and
medication taking during pregnancy).
- Physical examination including:
- General examination: weight, height, blood pressure,
pulse, respiratory rate, pallor, cynosis and lower limb
edema.
- pelviabdomenal examination for pelvic masses eg fibroid
uterus and ovarian dermoid cyst.
- Vaginal examination for cervical masses or vaginal
septum.
- Ultrasound examination:
- Pelvic ultrasonography: to assess Ovarian masses or
fibroid uterus.
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131
- All patients had undergone HSG to exclude uterine
synachie, tubal obstruction and uterine anomalies.
- 3D vaginal ultrasound to exclude congenital uterine
anomalies such as (T shaped uterus, bicornate or septate
uterus) if suspected by HSG.
- Hysteroscopy to exclude uterine synachie and uterine
Anomalies suspected by HSG.
Laboratory investigations before pregnancy:
- Complete blood count.
- Fasting, 2 hour postprandial blood sugar HbA1c.
- TSH, freeT3, T4.
- Investigation to exclude other causes of recurrent
miscarriage as (anticardolipin Abs, lupus anticoagulants)
- Antithyroid Abs and Anti nuclear Abs.
- When to start treatment:
- Folic acid (0.5 mg) was started in a period of 3 months
before conception in the two groups.
- Sildenafil citrate was started preconception from the
LMP starting from the last day of menses and repeated
till the patient become pregnant; (dose: 25 mg; vaginal
tablets, 4 times/day for 24 days) (El-Far et al., 2009).
When patient become pregnant:
- Assessment of gestational age by knowing LMP or first
trimesteric ultrasound.
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Antenatal care:
8. Antenatal care visit every 2 weeks: 1st visit was after
missed period.
9. Follow up for symptoms vaginal bleeding, hyperemesis,
weight gain, pelvic pain during each visit.
10. Transvaginal ultrasound to determine the number, site of
gestational sac at 6 weeks to determine fetal pole and
fetal pulsation.
11. Measurement of nuchal fold thickness between 11 and 14
weeks.
12. Measurement of cervical canal length by transvaginal
ultrasound at16 to18 weeks
13. Detailed anomaly scan at18 to21 week.
14. Uterine artery Doppler to measure uterine artery resistance
index and pulsitility index at 20 weeks.
Laboratory investigation during pregnancy at booking
visit:
Complete blood count.
Blood group and RH.
Viral markers hepatitis B, C and HIV.
Rubella IgG
Fasting, 2hr postprandial blood sugar.
Lupus anticoagulant, anticardiolipin IgG, IgM if was not
done before pregnancy.
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133
Antinuclear antibody test (ANA) if was not done before
pregnancy.
Complete urine analysis.
There was no statistically significant difference between
the study groups regarding demographic data (age, parity and
BMI).
There was also no statistically significant difference
between both study groups regarding transvaginal measurement
of cervical length.
This study results showed a statistically significant
decrease in group I from the group II according to uterine artery
resistant index at 20 weeks Mean±SD (0.54±0.14 versus
0.66±0.24).
This study showed a statistically significant decrease
in group I from the group II according to uterine artery
pulsatility index at 20 weeks Mean±SD (0.62±0.17 versus
0.77±0.12).
This study showed a highly statistically significant
difference between groups according to fetal viability till 20
weeks.
Also this study showed beneficial effect of sildenafil
citrate in the management of early recurrent unexplained
pregnancy loss.
In conclusion, our study showed that use of sildenafil
citrate decrease rate of recurrent unexplained pregnancy loss