Recurrent Miscarriage Guidelines

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Recurrent Miscarriage Guidelines Powered By Docstoc
					Recurrent Miscarriage

 Dr Muhammad El Hennawy
 Ob/gyn specialist
 Rass el barr central hospital and
      dumyat specialised hospital
 Dumyatt – EGYPT

A recurrent miscarriage is 3 or more
 consecutive, spontaneous
 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
    live birth,

   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 ,
                  habitual miscarriages,
                  recurrent abortions ,
                  recurrent miscarriages.
   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
    pregnancy losses
                 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
           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.

                 Explained                                          Un-explained

factors                                           Infective   Enviromental
                        Endocrine                  agents       factors

            factors                 Immune           Inhereted
                                     factors       Thrombophilic    Bacterial
                                                       defect       Vaginosis

          Body     Cervix

  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.
Genetic factors
 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
  unbalanced translocation.
   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
    balanced translocation.
           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
   and photographed.
The photograph is then rearranged to show the paired
  chromosomes. Size, shape and banding pattern are
  used to pair up the chromosomes.
   Anatomical factors

One in six to ten women with recurrent
 miscarriages has a structural defect
  like uterine septum or adhesions
 Hysterosalpingogram (HSG)
 two dimensional pelvic ultrasound
  with (or without)
 3D Ultrasound
 Laparoscopy
 Hysteroscopy
   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.
           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
   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
   uterus.
     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
    three-dimensional ultrasound
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 weakness
   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
Endocrine factors
       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
  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.
               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.
        Antithyroid antibodies
   Routine screening for thyroid
    antibodies in women with recurrent
    miscarriage is not recommended.
     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.
   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.
          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
Infective agents
   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
Environmental factors
   Exposture to noxious or toxic substances are
    known to be associated with recurrent
    miscarriage ( social drugs, cigarretes,alcohol
    and caffeine ,anaestetic gases,petrolium
    products )
   Unexplained recurrent
  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
    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.
       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
      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
  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
           If all of the above have been
   (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
            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 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
    when necessary.
                Emprical treatment
   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
   Subcutaneous hepaein
   Folic acid
   Progesterone
   Solcoseryl(increase oxygen supply)
   Nitroglycerin (increase implantation by increase uterine blood flow)
   tocolytic
          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
   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