RECURRENT MISCARRIAGE AN EVIDENCE BASED APPROACH

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RECURRENT MISCARRIAGE AN EVIDENCE BASED APPROACH

• 6th Annual Congress
• RAS EL BAR 7- 2003

Dr Mahdy El- Mazzahy Damietta General
Hospital
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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.

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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

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How common is recurrent miscarriage?
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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.

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Investigations and treatments
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1-Genetic factors (parental karyotypic
abnormalities)

• In approximately 35 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.

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1-Genetic factors (parental karyotypic
abnormalities)

• Genetic counselling offers the couple-
• A prognosis for future pregnancy
• Familial chromosomal studies
• Counselling where there is a 510 chance of a
  pregnancy with an unbalanced translocation
• Recently, preimplantation genetic diagnosis has
  been explored as a treatment option for
  translocation carriers.

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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
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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.

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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
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2-Anatomical factors
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2-Anatomical factors

• The routine use of hysterosalpingography as a
  screening test for uterine anomalies is
  questionable. It is associated with -
• Patient discomfort
• Carries a risk of pelvic infection and radiation
  exposure
• No more sensitive than the non-invasive pelvic
  ultrasound with (or without) Sonohysterography.

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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.

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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.

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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
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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
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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.
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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

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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
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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
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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
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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)
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4-Immunological causes(Antithyroid antibodies)

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

Grade B
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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

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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.

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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
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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
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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
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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.

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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
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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.

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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.

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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
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6- 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
  thrombosis.

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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
• However three uncontrolled studies have
  suggested that heparin therapy may improve the
  live birth rate for these women..

Cochrane Library, 2 2003
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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.

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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.

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Recommendations
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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 .

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Recommendations

• It is recommended that the investigation of
  recurrent miscarriage should include
• peripheral blood karyotyping in both partners .
• karyotyping of all fetal products.
• A pelvic ultrasound scan to assess the uterine
  cavity.

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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.

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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.

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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.

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• Thank you