early pregnancy complications : management of recurrent miscarriages Flashcards

1
Q

Define recurrent miscarriage

A

Two or more spontaneous pregnancy losses before 20 weeks of gestation. Early miscarriage is clinically distinct from losses after 20 weeks or premature deliveries.

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2
Q

When are investigations typically initiated for recurrent miscarriage?

A

Investigations are initiated when there are:

  1. Three or more first trimester losses
  2. Two or more second trimester losses
  3. Any combination of the above
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3
Q

What is the incidence of spontaneous miscarriage and recurrent miscarriage?

A
  • Spontaneous miscarriage: 15% of clinically recognized pregnancies
  • Two consecutive miscarriages: affects 5% of couples trying to conceive
  • Three or more miscarriages: affects 1% of couples
  • Note: These rates are higher than expected by chance alone, suggesting specific causes
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4
Q

What are the main categories of causes (aetiology) for recurrent miscarriage?

A
  1. Genetic causes
  2. Anatomic defects (congenital and acquired)
  3. Endocrine abnormalities
  4. Immunological abnormalities
  5. Thrombophilia
  6. Reproductive tract infections
    7.Metabolic and toxic factors
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5
Q

What are the genetic findings in first and second trimester miscarriages? ( for genetic causes )

A

First trimester: 50% have abnormal genetic material

Second trimester: 20% have abnormal genetic materia

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6
Q

wat is the common finding in genetic causes of recurrent miscarriage?

A

Most common finding: chromosomal aneuploidy (presence of abnormal number of chromosomes in a cell)

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7
Q

what is important about finding Finding aneuploid conceptus after miscarriage ?

A

Finding aneuploid conceptus does not increase risk of subsequent miscarriage with same anomaly

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8
Q

What is the significance of structural genetic abnormalities in recurrent miscarriage?

A

Found in 3-5% of couples with 2+ recurrent miscarriages

  • Most common type: balanced translocation
  • Affects one or both partners
  • More commonly associated with recurrent miscarriage than aneuploidy
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9
Q

What are the congenital anatomic defects associated with recurrent miscarriage?

A

Most common: septate and bicornuate uteri

Account for ~2% of all recurrent pregnancy losses as sole cause
Often associated with cervical incompetence

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10
Q

why is it important to look at other causes as well when considering anatomical anomalies as cause of miscarriage ?

A

Can still have satisfactory obstetric outcomes, so other causes must be investigated

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11
Q

What are the acquired anatomic defects that can cause recurrent miscarriage?

A

1.Adhesions and synechiae (Asherman’s syndrome) - > may cause recurrent miscarriage secondary to a loss of endometrial tissue, which is vital in sustaining fetal growth.

  1. Fibroids (submucous type)-> — if submucous and impinging on the endometrium they may be a cause of recurrent pregnancy loss, probably secondary to an alteration in endometrial blood flow.
  2. Acquired cervical incompetence->Diagnostic criteria not firmly established
  3. DES-related abnormalities (historical)-> related abnormalities may also result in recurrent losses secondary to induced uterine malformations. This is largely of historical significance though, as DES is not used in current clinical practice.
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12
Q

Give examples of endocrine dysfunction that cause recurrent miscarriage

A
  1. thyroid dysfunction
  2. DM
    3.Luteal phase defect
  3. PCOS
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13
Q

How does diabetes affect miscarriage risk?

A

Poorly controlled diabetes in first trimester (elevated HbA1c) increases spontaneous miscarriage risk 2-3 fold

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14
Q

What is Luteal Phase Defect?

A

Definition: Insufficient development of secretory endometrium

Causes:

  1. Inadequate progesterone from poorly developed corpus luteum
  2. Endometrial failure to respond to adequate progesterone
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15
Q

how is the luteal phase defect diagnosed?

A

Diagnosis: Gold standard is endometrial biopsy on two occasions showing “out of phase” endometrium lagging by 2 days
Note: No consensus on pathophysiology, diagnosis, or treatment

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16
Q

What are the key thyroid-related facts in recurrent miscarriage?

A

Screening for thyroid disease is only indicated if the patient is symptomatic. Not routinely recommended for asymptomatic patients.

17
Q

How does PCOS relate to recurrent miscarriage?

A

Relationship is controversial

  • LH hypersecretion implicated as risk factor
  • Pre-pregnancy LH suppression not proven to improve outcomes
  • Possible mechanism: increased plasminogen activator inhibitor (PAI) secretion
  • Research ongoing for treatment options
18
Q

what types of immunological abnoormalities can cause recurrent miscarriages ?

A
  1. Autoimmune -> primary and secondary antiphospholipid syndromes , conditions with ANA ( SLE,Sjogren’s,polymyositis
  2. Alloimune
  3. Thrombophilia
19
Q

What are the key features of antiphospholipid antibodies in pregnancy?

A

In pregnancy, phospholipids act like a sort of “glue” that holds the dividing cells together and are necessary for the growth of the placenta into the wall of the uterus. Therefore Antibodies to these phospholipids are associated with an increased risk of miscarriage.

20
Q

What is Primary Antiphospholipid Syndrome?

A

Primary antiphospholipid syndrome is diagnosed in the presence of antiphospholipid antibodies and adverse pregnancy outcome or vascular thrombosis.

Adverse outcomes include:
* 3 or more consecutive miscarriages before ten weeks,
* one or more morphologically normal fetal death after the 10th week of gestation, and
* one or more pre-term births before the 34th week of gestation due to severe pre-eclampsia, eclampsia or placental insufficiency.

21
Q

how is secondary antiphospholipid syndrome diagnosed ?

A

Secondary antiphospholipid syndrome is diagnosed when antiphospholipid syndrome exists
along with a chronic inflammatory condition like systemic lupus erythrematosus (SLE).

22
Q

What antibodies are important in both Primary and Secondary Antiphospholipid Syndrome?

A

Three key antibodies:

  1. Lupus anticoagulant (LA)
  2. Anticardiolipin antibodies (ACA)
  3. Anti-beta 2 glycoprotein-1 antibodies
23
Q

What is the pathogenesis of pregnancy loss in Antiphospholipid Syndrome?

A
  1. Placental thrombosis and infarction likely due to:Decreased prostacyclin (PGI2) - a natural anti-thrombotic and vasodilator
    OR Platelet damage with increased adhesiveness
  2. Results in impaired placental function and pregnancy loss
24
Q

What is the relationship between ANA (antinuclear antibodies) and recurrent miscarriage?

A

Associated with recurrent miscarriage

  • React against normal cell nucleus components
  • Present in various autoimmune diseases (SLE, Sjogren’s, polymyositis)
  • May indicate underlying autoimmune process affecting placental development
25
Q

why is ANA is not recommended for routine testing when there is miscarriage ?

A

Not recommended for routine testing as elevated levels also occur in normal population

26
Q

What are the characteristics of alloimmune causes of recurrent miscarriage?

A

Involves abnormal maternal immune response

Target: Antigens on placental or fetal tissue
Status: Treatment modalities still under research
Note: Further research needed before treatments can be recommended

27
Q

what is thrombophilia ?

A
  • Hereditary condition affecting natural anticoagulants
28
Q

hat are the key features of thrombophilia in recurrent miscarriage?

A

Clinical features:

  • Thromboembolic disease in young adults (<50y)
  • No other risk factors present
  • Associated with second trimester miscarriage
  • Involves abnormalities in protein C, protein S, and antithrombin III
  • Mechanism: Causes retroplacental thromboses and placental infarction
29
Q

What infectious agents have been studied in recurrent miscarriage?

A

Traditionally implicated organisms:

  • Mycoplasma
  • Ureaplasma
  • Listeria
  • Toxoplasmosis
  • Chlamydia
    Note: None definitively proven to cause recurrent miscarriage

Special consideration: - Bacterial vaginosis

Associated with second trimester miscarriage and preterm delivery
Early treatment may prevent preterm birth in at-risk women

30
Q

What is hyperhomocysteinemia and its relationship to recurrent miscarriage?

A

An abnormality in folate metabolism

Characterized by:

  • Methionine intolerance
  • High homocysteine concentrations

Has been widely associated with recurrent miscarriage

31
Q

How does Wilson’s Disease affect pregnancy outcomes?

A

Associated with exceedingly high miscarriage rate

Cause: Embryotoxic effect of copper
Important note: Extremely rare condition

32
Q

What is the relationship between smoking/alcohol and recurrent miscarriage?

A

Overall influence is very small in recurrent miscarriage population

  • Only heavy users show slightly increased risk
  • Not a major contributing factor for most patients
33
Q

What is known about radiation exposure and recurrent miscarriage?

A

Clear association with increased risk of recurrent miscarriage

Historical evidence: -
- Demonstrated after Chernobyl disaster
- Represents a direct toxic effect on pregnancy