Dr Muhammad El Hennawy
Rass el barr central hospital and
dumyat specialised hospital
Dumyatt – EGYPT
A recurrent miscarriage is 3 or more
pregnancy losses, under 20 week
gestation from the last menstrual period
, by the same partner.
Primary recurrent pregnancy loss"
refers to couples that have never had a
while "secondary RPL" refers to those
who have had repetitive losses
following a successful pregnancy
a woman who had a
miscarriage,instead of getting sympathy
and support, is made to feel that it is
somehow her fault
It is all too common to find recurrent
miscarriges leading to divorce
The medical term 'spontaneous abortion'
should be replaced with the term
Other names : recurrent pregnancy loss (RPL),
habitual abortions ,
recurrent abortions ,
10–15% of all clinically recognised pregnancies
end in a miscarriage
the theoretical risk of three consecutive
pregnancy losses that expected by chance
alone is 0.34%.
This incidence is greater than that expected by
chance alone---Recurrent miscarriage affects
1% of all women ---Hence, only a proportion of
women presenting with recurrent miscarriage
will have a persistent underlying cause for their
Advanced maternal age
adversely affects ovarian function, giving rise
to a decline in the number of good quality
oocytes, resulting in chromosomally abnormal
conceptions that rarely develop further.
. previous number of miscarriages
Recurrent miscarriage is a heterogeneous
condition that has many possible causes;
more than one contributory factor may
underlie the recurrent pregnancy losses.
each may have had a different cause.
factors Infective Enviromental
Endocrine agents factors
factors Immune Inhereted
factors Thrombophilic Bacterial
Paternal Cytogenetic anomalies
karyotyping Of miscarriage
Investigations and treatments
Recent information indicates that women should look into RPL testing
after two losses when it used to be common to wait until three. This is
especially important for women in their 30s and 40s
Diagnosis and investigation
EPAUs should use and develop diagnostic and
therapeutic algorithms of care.
In particular, these should include management of
'suspected ectopic pregnancy' (including serum hCG)
and the 'indeterminate' ultrasound scan.
EPAUs should have access to transvaginal ultrasound
with staff appropriately trained in its use.
Non-sensitised rhesus (Rh) negative women should
receive anti-D immunoglobulin in the following
situations: ectopic pregnancy, all miscarriages over 12
weeks (including threatened), all miscarriages where
the uterus is evacuated, and for threatened
miscarriages under 12 weeks when bleeding is heavy or
associated with pain.
All couples with a history of recurrent
miscarriage should have peripheral blood
karyotyping performed. The finding of an
abnormal parental karyotype should
prompt referral to a clinical geneticist.
3–5% of couples with recurrent miscarriage,
one of the partners carries a balanced
structural chromosomal anomaly
5–10% chance of a pregnancy with an
In all couples with a history of recurrent
miscarriage cytogenetic analysis of the
products of conception should be performed
if the next pregnancy fails.
an abnormal embryo, which is incompatible with
life, e.g. chromosomal abnormalities or structural
If the karyotype of the miscarried pregnancy is
abnormal, there is a better prognosis in the next
Cytogenetic testing is an expensive tool and
should be reserved for patients who have
undergone treatment in the index pregnancy or
have been participants in a research trial
Fetal chromosomal abnormalities
This may be due to abnormalities in the
egg, sperm or both. The most common
chromosomal defects are
Chromosome Testing on Fetal (Miscarriage)
This can only be done right at the time of miscarriage.
It is an analysis of the genetic makeup of the fetus.
It can indicate genetic problems that lead to RPL.
Many miscarriages are caused by chromosomal
abnormalities that are unlikely to repeat. To know if
the problem is likely to recur, it is necessary to study
the genetics of both parents as well.
Karyotyping of Parents
each Chromosome analysis of blood of both parents.
It can show if there is a potential problem with one of
the parents that leads to miscarriage, but often has to
be done in conjunction with fetal testing to provide
These tests help rule out the 3% or so of partners
that carry a "hidden" chromosomal problem called a
KARYOTYPING , HOW?
It is A display of an individual’s chromosome pairs.
Process : Sample of cells is taken, usually blood cells.
Cells are chemically stimulated to undergo mitosis.
Mitosis is stopped at metaphase.
Chromosomes are separated out,
viewed with a microscope
The photograph is then rearranged to show the paired
chromosomes. Size, shape and banding pattern are
used to pair up the chromosomes.
One in six to ten women with recurrent
miscarriages has a structural defect
like uterine septum or adhesions
two dimensional pelvic ultrasound
with (or without)
The reported prevalence of uterine anomalies in
recurrent miscarriage populations range between
1.8% and 37.6%.
The prevalence of uterine malformations appears to
be higher in women with late miscarriages compared
with women who suffer early miscarriages but this
may be related to the cervical weakness that is
frequently associated with uterine malformation.
untreated uterine anomalies has a term delivery rate
of only 50%.
Open uterine surgery is associated with postoperative
infertility and carries a significant risk of uterine scar
rupture during pregnancy. These complications are
less likely to occur after hysteroscopic surgery but no
randomised trial assessing the benefits of surgical
correction of uterine abnormalities on pregnancy
outcome has been performed.
an abnormal or irregularly shaped uterus.
Sometimes the uterus has an extra wall down its
centre, which makes it look as if it is divided into
two (bicornuate or septate uterus)
a septate uterus Where as a partial septum
increases the risk to 60%-75%; a total septum
carries a risk for loss of up to 90%.
Today a relatively simple surgical procedure can
remove a uterine septum
or it may have only developed one half
It is not clear if such problems cause recurrent
If fibroids are detected on the inside of
the uterus (termed submucous fibroids)
and distort the uterine lining, they are a
significant cause of reproductive problems
and should be removed. It is less clear
whether fibroids in the wall of the uterus
cause reproductive problems
scar tissue in the uterus
scar tissue in the uterus which may hinder
implantation or growth of the fetus.
The routine use of hysterosalpingography as a
screening test for uterine anomalies in women
with recurrent miscarriage is questionable.
It is associated with patient discomfort,
carries a risk of pelvic infection and radiation
and is no more sensitive than the non-invasive
two dimensional pelvic ultrasound assessment
of the uterine cavity with (or without)
Sonohysterography when performed by skilled
and experienced personnel.
Hysterosonography provides a sensitive
and specific screening tool for evaluating
the uterine cavity and it could be an
accurate alternative to HSG in screening
for uterine abnormalities
It is sometimes possible to see abnormalities inside the uterus at
the time of a scan, especially a
vaginal scan. A scan will also enable the ovaries to be examined at
the same time. Occasionally
polycystic ovaries are diagnosed by ultrasound scan (see above).
Some units will offer a scan and an examination of the inside of the
uterus at the same time - saline
installation sonography (SIS). A small plastic tube is passed
through the cervix and a water-like
solution injected through it. The scan can determine whether there
is any abnormality inside the
All women with recurrent
miscarriage should have a
pelvic ultrasound to assess
uterine anatomy and
Two dimensional pelvic ultrasound
assessment of the uterine cavity with
(or without) Sonohysterography
The diagnostic value of three-dimensional
ultrasound has been explored and appears
Since three-dimensional ultrasound offer
both diagnosis and classification of uterine
malformation its use may obviate the need
for diagnostic hysteroscopy and
This investigation, performed under
general anaesthetic, examines the inside
of the uterus with a thin
telescope (3-5 mm in diameter) . By
inserting this telescope through the cervix
and into the uterus,
the doctor can see the shape of the uterus
and examine its lining.
Cervical cerclage is associated with potential
hazards related to the surgery and the risk of
stimulating uterine contractions and hence
should only be considered in women who are
likely to benefit.
Cervical weakness is often over-diagnosed as a cause
of mid-trimester miscarriage.
The diagnosis is usually based on a history of late
miscarriage, preceded by spontaneous rupture of
membranes or painless cervical dilatation.
Transvaginal ultrasound assessment of the cervix
during pregnancy may be useful in predicting preterm
birth in some cases of suspected cervical weakness
Transabdominal cerclage has been advocated as a
treatment for second-trimester miscarriage and the
prevention of early preterm labour in selected women
with previous failed transvaginal cerclage and/or a very
short and scarred cervix
Routine screening for occult
diabetes and thyroid disease with
oral glucose tolerance and thyroid
function tests in asymptomatic
women presenting with recurrent
miscarriage is uninformative
well-controlled diabetes mellitus is not a risk
factor for recurrent miscarriage, nor is treated
There is insufficient evidence to
evaluate the effect of progesterone
supplementation in pregnancy to
prevent a miscarriage
hormonal treatments for luteal phase deficiency concluded that
the benefits are uncertain the low progesterone levels that
have been reported in early pregnancy loss may reflect a
pregnancy that has already failed. Exogenous progesterone
supplementation should only be used in the context of
randomised controlled trials.
Progesterone doesn't prevent miscarriages. Miscarriages
happen for many reasons,
but lack of progesterone as a cause for miscarriage is not
proven. The low progesterone levels found in pregnancies
which go on to become miscarriages is a sign that the
pregnancy is already failing
There is insufficient evidence to
evaluate the effect of human
chorionic gonadotrophin (hCG) in
pregnancy to prevent miscarriage.
early pregnancy hCG supplementation failed to
show any benefit in pregnancy outcome
Prepregnancy suppression of high
luteinising hormone (LH)
concentration among ovulatory
women with recurrent miscarriage
and polycystic ovaries who
hypersecrete LH does not improve
the live birth rate
the outcome of pregnancy without pituitary
suppression is similar to that of patients
without raised LH.
Polycystic ovary morphology itself does
not predict an increased risk of future
pregnancy loss among ovulatory women
with a history of recurrent miscarriage
who conceive spontaneously.
pelvic ultrasound criteria, is significantly higher among
women with recurrent miscarriage (41%) when
compared with the general population (22%).
However, despite this high prevalence, polycystic
ovary morphology itself does not predict an increased
risk of future pregnancy loss among ovulatory women
with a history of recurrent miscarriage who conceive
There is insufficient evidence to
assess the effect of
hyperprolactinaemia as a risk
factor for recurrent miscarriage.
One in ten women with recurrent miscarriages show evidence
of auto immune factors on investigation
As much as 40 percent of unexplained infertility may be the
result of immune problems, as are as many as 80 percent of
"unexplained" pregnancy losses. Unfortunately for couples
with immunological problems, their chances of recurrent loss
increase with each successive pregnancy.
Routine screening for thyroid
antibodies in women with recurrent
miscarriage is not recommended.
To diagnose APS it is mandatory that the
patient should have two positive tests at
least six weeks apart for either lupus
anticoagulant or anticardiolipin (aCL)
antibodies of IgG and/or IgM class present in
medium or high titre.
Adverse pregnancy outcomes include
(a) three or more consecutive miscarriages before ten
weeks of gestation,
(b) one or more morphologically normal fetal deaths
after the tenth week of gestation and
(c) one or more preterm births before the 34th week
of gestation due to severe pre-eclampsia, eclampsia
or placental insufficiency.
Currently there is no reliable evidence to
show that steroids improve the live birth rate
of women with recurrent miscarriage
associated with aPL when compared with
other treatment modalities; their use may
provoke significant maternal and fetal
In women with a history of recurrent
miscarriage and aPL, future live birth rate is
significantly improved when a combination
therapy of aspirin plus heparin is prescribed.
Pregnancies associated with aPL treated
with aspirin and heparin remain at high risk
of complications during all three trimesters.
Immunotherapy, including paternal
cell immunisation, third-party donor
leucocytes, trophoblast membranes
and intravenous immunoglobulin
(IVIG), in women with previous
unexplained recurrent miscarriage
does not improve the live birth rate
TORCH (toxoplasmosis rubella,
cytomegalovirus and herpes simplex
virus), other [congenital syphilis and
viruses], screening is unhelpful in the
investigation of recurrent miscarriage.
For an infective agent to be implicated in the
aetiology of repeated pregnancy loss, it must
be capable of persisting in the genital tract and
avoiding detection or must cause insufficient
symptoms to disturb the women.
Toxoplasmosis, rubella, cytomegalovirus,
herpes and listeria infections do not fulfil these
criteria and routine TORCH screening should be
Screening for and treatment of
bacterial vaginosis in early
pregnancy among high risk women
with a previous history of second-
trimester miscarriage or
spontaneous preterm labour may
reduce the risk of recurrent late
loss and preterm birth.
Group B Streptococcus
Pre and Post-conceptional, broad-
spectrum intravenous antibiotic therapy
was used in patients with multiple
Although this is a relatively small series and
does not establish a cause and effect
relationship between Group B Streptococcus and
habitual abortions, the beneficial effects of
antibiotic therapy is unquestionable
Inherited thrombophilic defects
Inherited thrombophilic defects,
including activated protein C resistance
(most commonly due to factor V Leiden gene
mutation), deficiencies of protein C/S and
antithrombin III, hyperhomocysteinaemia and
prothrombin gene mutation,
are established causes of systemic
Exposture to noxious or toxic substances are
known to be associated with recurrent
miscarriage ( social drugs, cigarretes,alcohol
and caffeine ,anaestetic gases,petrolium
In about half the women in the research
studies, no cause could be found, so no
specific treatment could be given.
However, this group responded very well to
a programme which removed as many stress
factors as possible from their lives, resulting
in an 80% success rate with the subsequent
Women with unexplained recurrent
miscarriage have an excellent prognosis
for future pregnancy outcome without
pharmacological intervention if offered
supportive care alone in the setting of a
dedicated early pregnancy assessment
After all these investigations 50% of recurrent
aborters will be found to have no
abnormalities and these should be attributed
to chromosomal defect in the conceptus.
According to the American College of
Obstetricians and Gynecologists
cultures for bacteria and viruses
glucose tolerance testing
antibodies to infectious agents
paternal human leukocyte antigen status, or maternal
are not beneficial and, therefore,
are not recommended in the evaluation of
otherwise normal women with recurrent pregnancy loss.
Things unlikely to cause recurrent
Retroversion - or backward tilting of the uterus.
Infection - such as toxoplasmosis, listeria, brucella, chlamydia,
herpes simplex and cytomegalovirus.
Endocrine or metabolic disease - hypothyroidism
(underactive thyroid), diabetes mellitus, Crohn's disease, sickle
cell or endometriosis.
Occupational exposures - very little reliable evidence exists
for things such as herbicide spraying, electromagnetic fields,
chemical inhalation, anaesthetic gases or VDU usage.
Not resting enough - bedrest doesn't alter whether you
miscarry or not. Nor does working when you're pregnant,
exercise, making love or flying.
Miscarriages, like infertility, is a problem of a
couple and they should be seen together. The
majority can be reassuared.
most cases, neither a woman nor her
doctor can do anything to prevent a
treatment for pregnancy loss
Evidence-based medicine (EBM) has not
succeeded in giving patients and
physicians the data they need to choose
(or not choose) a therapy in the field of
If any of the above tests should
come back indicating an underlying
reason for the problem
treatment is direced at the cause
eg : genetic counselling,
removal of fibroids,
If all of the above have been
(as they will do in most cases), the diagnosis is recurrent miscarriage of
the use of empirical treatment in women with unexplained recurrent
miscarriage is unnecessary and should be resisted
for both partners to be as healthy as possible before
she conceive (avoid drugs, alcohol, chemicals, etc)
and to get any other medical conditions under control.
The only intervention to have demonstrated benefit is serial ultrasound
scans in the early months of pregnancy.
It is certainly not unreasonable to expect this psychological support to
improve outcome given the close interaction between the higher areas of
the mind and the delicately balanced hormonal system.
Education and reassuarance with these good statistical odds
Education about smoking, alcohol and drug abuse is also important
The value of psychological support in improving
pregnancy outcome has not been tested in the form of a
randomised controlled trial. However, data from several
non-randomised studies86–88 have suggested that
attendance at a dedicated early pregnancy clinic has a
beneficial effect, although the mechanism is unclear
All professionals should be aware of the
psychological sequelae associated with
miscarriage and should provide support and
follow-up, as well as access to formal counselling
the use of empirical treatment in women with unexplained recurrent
miscarriage is unnecessary and should be resisted
Some doctors give treatment like
Low dose asprin
Solcoseryl(increase oxygen supply)
Nitroglycerin (increase implantation by increase uterine blood flow)
Treatment of miscarriage
Surgical uterine evacuation for miscarriage should be
performed using suction curettage.
All at risk women undergoing surgical uterine
evacuation for miscarriage should be screened for
Medical and expectant methods are also effective in the
management of confirmed miscarriage.
Medical and expectant management should be offered
only in units where patients have access to 24-hour
telephone advice and immediate admission can be
Tissue obtained at the time of miscarriage should be
examined histologically to confirm pregnancy and to
exclude ectopic pregnancy or gestational trophoblastic
A woman who has suffered a single
sporadic miscarriage has an 80% chance
and a woman with three consecutive
miscarriages a 60% chance of her next
pregnancy being successful