RECURRENT MISCARRIAGE AN EVIDENCE BASED APPROACH

Document Sample
RECURRENT MISCARRIAGE AN EVIDENCE BASED APPROACH Powered By Docstoc
					RECURRENT MISCARRIAGE
  AN EVIDENCE BASED
      APPROACH




     6th Annual Congress
    “RAS EL BAR ” 7- 2003

  Dr Mahdy El- Mazzahy
 Damietta General Hospital
 Introduction and definition
• An unexpected miscarriage is a
  distressing problem that can
  shatter dreams.
• Two or more can be
  devastating. But now there is
  hope, and a solution.
  Introduction and definition
• Recurrent miscarriage is defined as the
  loss of three or more consecutive
  pregnancies before viability (20w).
• Some clinicians favour changing the
  definition to two or more consecutive
  losses, but the efficacy of commencing
  investigations after two losses has not
  been established
How
common is
recurrent
miscarriage?
       How common is recurrent
            miscarriage?
• The incidence of clinical miscarriage is 15%,
• So the theoretical risk of three consecutive
  pregnancy losses is 0.34%.
• But the incidence of recurrent miscarriage is
  greater than that expected by chance alone.
  about 1%. .
• We can conclude that at least one third of women
  who experience recurrent miscarriage do so
  because of successive episodes of bad luck and
  THE OTHER will have a persistent underlying
  cause for their pregnancy losses.
Investigations and
    treatments
       1-Genetic factors
     (parental karyotypic abnormalities)
• In approximately 3–5% of couples with
  recurrent miscarriage, one of the
  partners carries a chromosomal
  abnormality, most commonly a
  balanced reciprocal or Robertsonian
  translocation.
• According to a study in the June issue
  of Obstetric &Gynecology 2003
  Recurrent pregnancy loss may be
  associated with defective sperm.
       1-Genetic factors
   (parental karyotypic abnormalities)
Genetic counselling offers the couple:-
• A prognosis for future pregnancy
• Familial chromosomal studies
• Counselling where there is a 5–10%
  chance of a pregnancy with an
  unbalanced translocation
• Recently, preimplantation genetic
  diagnosis has been explored as a
  treatment option for translocation
  carriers.
        1-Genetic factors
   (parental karyotypic abnormalities)
                  Grade C
• 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.
                     RCOG May 2003
        1-Genetic factors
 (chromosome abnormality of the fetus)

• Recurrent pregnancy loss may be
  due to an abnormal embryo.
• The patient can be reassured that,
  a chromosome abnormality of the
  fetus is a random event and not a
  recurring cause of miscarriage and
  there is a better prognosis in the
  next pregnancy.
       1-Genetic factors
 (chromosome abnormality of the fetus)
                Grade C
• In all couples with a history of
  recurrent miscarriage cytogenetic
  analysis of the products of
  conception should be performed if
  the next pregnancy fails.
               RCOG May 2003
2-Anatomical factors
        2-Anatomical factors
The routine use of hysterosalpingography as a
   screening test for uterine anomalies is
   questionable. It is associated with :-
1. Patient discomfort
2. Carries a risk of pelvic infection and radiation
   exposure
3. No more sensitive than the non-invasive pelvic
   ultrasound with (or without)
   Sonohysterography.
     2-Anatomical factors

• All women with recurrent miscarriage
  should have a pelvic ultrasound to
  assess uterine anatomy and
  morphology
• The diagnostic value of three-D
  ultrasound has been explored and
  appears promising. and its use may
  obviate the need for diagnostic
  hysteroscopy and laparoscopy.
           2-Anatomical factors
                 (uterine septum)
• Open uterine surgery is associated with
  postoperative infertility and rupture scar during
  pregnancy.
• According to ACOG Women with recurrent
  miscarriage and uterine septum should undergo
  hysteroscopic surgery.
• No randomised trial assessing the benefits of
  surgical correction of uterine abnormalities on
  pregnancy outcome has been performed.
     2-Anatomical factors
         ( Cervical weakness )
• Cervical incompetence is often over-
  diagnosed as a cause of mid-trimester
  miscarriage.
• cerclage should only be considered
  when the history of miscarriage is
  preceded by spontaneous rupture of
  membranes or painless cervical
  dilatation.
                   RCOG May 2003
    2-Anatomical factors
         ( 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.
.                        Grade B
        2-Anatomical factors
              ( Cervical weakness )
• The use of a cervical stitch should not be
  offered to women at low or medium risk of mid
  trimester loss, regardless of cervical length by
  ultrasound
  The role of cervical cerclage for women who
  have short cervix on ultrasound remains
  uncertain as the numbers of randomised
  women are too few to draw firm conclusions.
                     The Cochrane Library, 2-2003.
3-Endocrine factors
(diabetes and thyroid)
• Routine screening for occult
  diabetes and thyroid disease
  with oral glucose tolerance and
  thyroid function tests in
  asymptomatic women
  presenting with recurrent
  miscarriage is not recommended
  3-Endocrine factors
  (progesterone)
• the low progesterone levels that have been
  reported in early pregnancy loss may reflect a
  pregnancy that has already failed.
• Progesterone supplements have been
  evaluated in clinical trials and have not been
  shown to be of any benefit and does not differ
  than placebo.
                             Grade A
3-Endocrine factors
(human chorionic gonadotrophin )
                Grade A
• There is not enough evidence to
  evaluate the use of HCG during
  pregnancy in order to prevent
  miscarriage in women with a history
  of unexplained recurrent miscarriage.
                    The Cochrane Library
3-Endocrine factors
(luteinizing hormone )
• It was thought that high levels of serum
  (LH) associated with PCOS caused
  chromosomally abnormal eggs, leading to
  an increased risk of miscarriage.
• However, recent studies have disproved
  that theory.
• suppression of LH does not improve the
  live birth rate for those women.
                             Grade A
3-Endocrine factors
(hyperprolactinaemia)
            Grade A
• There is insufficient
  evidence to assess the
  effect of
  hyperprolactinaemia as a
  risk factor for recurrent
  miscarriage.
                 (RCOG May 2003)
  4-Immunological causes
      (Antithyroid antibodies)


• Routine screening for
  thyroid antibodies in women
  with recurrent miscarriage is
  not recommended..
                     Grade B
  4-Immunological causes
    ( Antiphospholipid syndrome)
• Primary antiphospholipid
  syndrome (APS) refers to the
  association between
  antiphospholipid antibodies and
  adverse pregnancy outcome or
  vascular thrombosis.
• secondary APS. such as in
  systemic lupus erythematosus
   4-Immunological causes
      ( Antiphospholipid syndrome)
• Antiphospholipid antibodies are
  present in 15% of women with
  recurrent miscarriage. when
  compared with 2%. in women with a
  low risk obstetric history
• the live birth rate in pregnancies with
  no pharmacological intervention may
  be as low as 10%.
  4-Immunological causes
     ( 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 antibodies
           RCOG May 2003, grade C
    4-Immunological causes
    ( Antiphospholipid syndrome)
             • Grade A
• Currently there is no reliable
  evidence to show that steroids
  improve the live birth rate of
  women with recurrent
  miscarriage associated with
  aPL.              RCOG May 2003
     4-Immunological causes
     ( Antiphospholipid syndrome)
                   Grade A
• the live birth rate of those women
  increased to 40% when they are treated
  with low-dose aspirin only and this is
  significantly improved to 70% when
  they are treated with low-dose aspirin
  in combination with low-dose heparin.

                       RCOG May 2003
  4-Immunological causes
         ( Alloimmune factors )

There is no clear evidence to support
  the hypothesis that
• HLA incompatibility between couples,
• The absence of maternal leucocytotoxic
  antibodies or
• the absence of maternal blocking
  antibodies
are related to recurrent miscarriage.
     4-Immunological causes
      ( Alloimmune factors )
                Grade A
• Paternal cell immunization, third party
  donor leukocytes, trophoblast
  membranes, and intravenous immune
  globulin provide no significant
  beneficial effect over placebo in
  preventing further miscarriages
                    The Cochrane Library, 2 2003
   4-Immunological causes
    ( Alloimmune factors )
• SO The use of immunotherapy
  should no longer be offered to
  women with unexplained recurrent
  miscarriage and routine tests for
  HLA type and anti-paternal
  cytotoxic antibody should be
  abandoned.
           5-Infective agents
                    (TORCH )
• Any severe infection that leads to
  bacteraemia or viraemia can cause
  sporadic miscarriage. The role of
  infection in recurrent miscarriage is
  unclear.
• So TORCH (toxoplasmosis, other
  [congenital syphilis and viruses], rubella,
  cytomegalovirus and herpes simplex
  virus) screening is unhelpful in the
  investigation of recurrent miscarriage.
           5-Infective agents
          (bacterial   vaginosis )
                     Grad A
• 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, but not for first trimester
  miscarriage
                    Cochrane library 2-2003
  6- Thrombophilic defects
   Inherited thrombophilic defects,
   including:-
1. Activated protein C resistance (most
   commonly due to factor V Leiden gene
   mutation),
2. Deficiencies of protein C/S and
   antithrombin III,
3. Hyperhomocysteinaemia and prothrombin
   gene mutation,
  are established causes of systemic
  thrombosis.
  6- Thrombophilic defects
• The efficacy of thromboprophylaxis
  during pregnancy in these women, has
  not been assessed in randomised
  controlled trials.
• No completed trials up till now
                           Cochrane Library, 2 2003
• However three uncontrolled studies have
  suggested that heparin therapy may
  improve the live birth rate for these
  women..
Unexplained recurrent miscarriage

          Grade C
• Women with unexplained
  recurrent miscarriage
  have an excellent
  prognosis for future
  pregnancy outcome
  without pharmacological
  intervention if offered
  supportive care alone.
Unexplained recurrent miscarriage

• according to ACOG, Informative and
  sympathetic counseling appears to play an
  important role. About 60% of couples with
  unexplained recurrent pregnancy loss who
  do not receive treatment will have a
  successful pregnancy.
• This high success rate emphasizes the
  fact that the use of empirical therapy in
  women with no cause is unnecessary,
  potentially harmful and should be
  resisted.
Recommendations
       Recommendations
Things unlikely to cause recurrent miscarriage
• Retroversion - or backward tilting of the
   uterus.
• Infection - such as TORCH.
• Endocrine or metabolic disease -
   hypothyroidism (diabetes mellitus, Crohn's
   disease, sickle cell or endometriosis.
• Occupational exposures - such as herbicide
   spraying, electromagnetic fields, chemical
   inhalation, anaesthetic gases .
• Not resting enough .
      Recommendations
It is recommended that the
    investigation of recurrent
    miscarriage should include:
1. peripheral blood karyotyping in
    both partners .
2. karyotyping of all fetal products.
3. A pelvic ultrasound scan to
    assess the uterine cavity.
      Recommendations
4. Screening tests for antiphospholipid
  antibodies (both the lupus anticoagulant
  and anticardiolipin antibodies) performed
  on two separate occasions at least six
  weeks apart.
5.The place of all other investigations is
  unproven and such tests should only be
  performed in the context of research
  studies.
         Recommendations
• It is further recommended that the
  treatment should include:-
• Those with karyotypic abnormalities
  should be seen by a clinical geneticist.
• That women with persistently positive tests
  for antiphospholipid antibodies are offered
  treatment with low dose aspirin together
  with low dose heparin during pregnancy.
       Recommendations

• A sympathetic physician attitude is
  essential in caring for patients with
  pregnancy loss.
• That treatments of unproven benefit
  should be abandoned .
• That all future treatment options are
  evaluated in randomised controlled
  trials.