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Recurrent Miscarriage Guidelines

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... consecutive, spontaneous pregnancy losses, under 20 week ... Primary recurrent pregnancy loss' refers to couples that have never had a live birth, ... – PowerPoint PPT presentation

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Title: Recurrent Miscarriage Guidelines


1
Recurrent Miscarriage Guidelines
  • Dr Muhammad El Hennawy
  • Ob/gyn specialist
  • Rass el barr central hospital and
  • dumyat specialised hospital
  • Dumyatt EGYPT
  • www.geocities.com/mmhennawy

2
Definition
  • A recurrent miscarriage is 3 or more
    consecutive, spontaneous pregnancy losses, under
    20 week gestation from the last menstrual period
    , by the same partner.

3
  • Primary recurrent pregnancy loss" refers to
    couples that have never had a live birth,
  • while "secondary RPL" refers to those who have
    had repetitive losses following a successful
    pregnancy

4
  • 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

5
Terminology
  • The medical term 'spontaneous abortion' should be
    replaced with the term 'miscarriage'
  • Other names recurrent pregnancy loss (RPL),
  • habitual abortions ,
  • habitual miscarriages,
  • recurrent abortions ,
  • recurrent miscarriages.

6
Incidence
  • 1015 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 pregnancy
    losses

7
Risk factors
  • 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

8
possible causes
  • 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.

9
Recurent Miscarriage
Explained
Un-explained
Genetic factors
Infective agents
Endocrine
Enviromental factors
Anatomical factors
Immune factors
Inhereted Thrombophilic defect
Bacterial Vaginosis
Body
Cervix
C I
APS
Uterine anomalies
Paternal karyotyping
Cytogenetic Of miscarriage
10
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
11
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.

12
Genetic factors
13
  • 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.
  • 35 of couples with recurrent miscarriage, one
    of the partners carries a balanced structural
    chromosomal anomaly
  • 510 chance of a pregnancy with an unbalanced
    translocation.

14
  • 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 malformations.
  • If the karyotype of the miscarried pregnancy is
    abnormal, there is a better prognosis in the next
    pregnancy
  • 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

15
Fetal chromosomal abnormalities
  • This may be due to abnormalities in the egg,
    sperm or both. The  most common chromosomal
    defects are
  • Trisomy
  • Monosomy 
  • Polyploidy

16
  • Chromosome Testing on Fetal (Miscarriage) Tissue
  • 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 answers.
  • These tests help rule out the 3 or so of
    partners that carry a "hidden" chromosomal
    problem called a balanced translocation.

17
KARYOTYPING , HOW?
  • It is A display of an individuals 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
  • and photographed.
  • The photograph is then rearranged to show the
    paired chromosomes. Size, shape and banding
    pattern are used to pair up the chromosomes.

18
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19
Anatomical factors
  • One in six to ten women with recurrent
    miscarriages has a structural defect like uterine
    septum or adhesions

20
  • Hysterosalpingogram (HSG)
  • two dimensional pelvic ultrasound with (or
    without) Sonohysterography
  • 3D Ultrasound
  • Laparoscopy
  • Hysteroscopy

21
  • 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.

22
Congenital anomalies
  • 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
    (unicornuate uterus).
  • It is not clear if such problems cause recurrent
    miscarriage,

23
fibroids
  • 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

24
scar tissue in the uterus
  • scar tissue in the uterus which may hinder
    implantation or growth of the fetus.

25
Hysterosalpingography
  • 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
    exposure
  • 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.

26
Hysterosonography
  • 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

27
Ultrasound
  • 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
  • uterus.

28
All women with recurrent miscarriage should have
a pelvic ultrasound to assess uterine anatomy and
morphology
  • Two dimensional pelvic ultrasound assessment of
    the uterine cavity with (or without)
    Sonohysterography

29
three-dimensional ultrasound
  • The diagnostic value of three-dimensional
    ultrasound has been explored and appears
    promising.
  • Since three-dimensional ultrasound offer both
    diagnosis and classification of uterine
    malformation its use may obviate the need for
    diagnostic hysteroscopy and laparoscopy.

30
Hysteroscopy
  • 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.

31
Cervical weakness
32
  • 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

33
Endocrine factors
34
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
    thyroid dysfunction

35
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

36
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

37
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.

38
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 spontaneously.

39
There is insufficient evidence to assess the
effect of hyperprolactinaemia as a risk factor
for recurrent miscarriage.
40
Immune factors
  • 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.

41
Antithyroid antibodies
  • Routine screening for thyroid antibodies in women
    with recurrent miscarriage is not recommended.

42
Antiphospholipid syndrome
  • 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.

43
  • 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 morbidity.
  • 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.

44
Alloimmune factors
  • 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

45
Infective agents
46
  • 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 abandone

47
  • 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.

48
Group B Streptococcus
  • Pre and Post-conceptional, broad-spectrum
    intravenous antibiotic therapy was used in
    patients with multiple miscarriages
  • 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

49
Inherited thrombophilic defects
50
  • 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 thrombosis

51
Environmental factors
52
  • Exposture to noxious or toxic substances are
    known to be associated with recurrent miscarriage
    ( social drugs, cigarretes,alcohol and caffeine
    ,anaestetic gases,petrolium products )

53
Unexplained recurrent miscarriage
  • 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 pregnancy

54
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 unit. 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.
55
According to the American College of
Obstetricians and Gynecologists
  • cultures for bacteria and viruses
  • glucose tolerance testing
  • thyroid tests
  • antibodies to infectious agents
  • antithyroid antibodies
  • paternal human leukocyte antigen status, or
    maternal antiparental antibodies
  • are not beneficial and, therefore,
  • are not recommended in the evaluation of
    otherwise normal women with recurrent pregnancy
    loss.

56
Things unlikely to cause recurrent miscarriage
  • 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.

57
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58
Management
  • 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 miscarriage

59
Controversies surrounding 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 pregnancy loss

60
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,
  • cervical stitch

61
If all of the above have been excluded
  • (as they will do in most cases), the diagnosis is
    recurrent miscarriage of unknown cause
  • 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

62
Psychological support
  • 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 studies8688 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 when necessary.

63
Emprical treatment
  • the use of empirical treatment in women with
    unexplained recurrent miscarriage is unnecessary
    and should be resisted
  • BUT
  • Some doctors give treatment like
  • Low dose asprin
  • Subcutaneous hepaein
  • Folic acid
  • Progesterone
  • Solcoseryl(increase oxygen supply)
  • Nitroglycerin (increase implantation by increase
    uterine blood flow)
  • tocolytic

64
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
    Chlamydia trachomatis.
  • 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 arranged.
  • Tissue obtained at the time of miscarriage should
    be examined histologically to confirm pregnancy
    and to exclude ectopic pregnancy or gestational
    trophoblastic disease.

65
Fate
  • 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
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