Recurrent Miscarriage and Pre-Eclampsia

The following sections are included:

• Contents

• Preface

The following sections are included:

• INTRODUCTION

• SPONTANEOUS MISCARRIAGE
  • Introduction
  • Maternal Age
  • Subfertility
  • Psychological Stress
  • Body Mass Index
  • Infection
  • Nutritional Factors
  • Smoking and Alcohol
  • Maternal Disease

• RECURRENT MISCARRIAGE
  • Introduction
  • Endocrinal Factors
    • Progesterone
    • Human chorionic gonadotrophin
    • Luteinising hormone hypersecretion and polycystic ovarian syndrome
  • Anatomical Problems
    • Uterine anomalies
    • Cervical factors
  • Infection
  • Recurrent Aneuploidy
  • Thrombophilia
    • Inherited thrombophilia
    • Acquired thrombophilia
  • Immunological
  • Prognosis

• REFERENCES

The following sections are included:

• INTRODUCTION AND HISTORY

• DEFINITION

• INCIDENCE

• PATHOGENESIS
  • Placental Pathology
  • Genetic Factors
  • Immunological Factors
  • Oxidative Stress
  • Vasoactive Peptides
  • Prostaglandins
  • Glucose Metabolism and Insulin Resistance
  • Lipid Abnormalities
  • Thrombophilia
  • Environmental Factors
    • Smoking
    • Longevity of sexual cohabitation

• PRESENTATION
  • Hypertension
  • Renal
  • Haematological
  • Complicated Pre-eclampsia
    • HELLP syndrome (Haemolysis, Elevated Liver enzymes, Low Platelets)
    • Haemolytic uraemic syndrome (HUS)
    • Acute fatty liver of pregnancy (AFLP)
    • Cerebral haemorrhage
    • Eclampsia

• FETAL COMPLICATIONS

• TREATMENT
  • Treatment of the Cause
  • Prevention of the Disease
    • Antioxidants
    • Antiprostaglandins
    • Calcium supplementation
  • Treatment of the Disease
    • Antihypertensives
    • Anticonvulsants

• LONG-TERM COMPLICATIONS

• REFERENCES

Oxidative stress, which is defined as an imbalance between pro- and antioxidant forces resulting in a pro-oxidant insult, arises from either the increased production of reactive oxygen species (ROS) or from a deficiency in the protective antioxidant system. ROS have important functions in normal physiology but their overproduction can cause disease (Halliwell, 1993). There is a natural balance between free radical production and natural antioxidant body defences but a cellular redox imbalance leads to oxidative stress and tissue injury. Endogenous and exogenous factors contribute to the production of highly reactive free radicals that can oxidise biomolecules and lead to cell death and tissue injury. The most important free radicals are oxygen and its radical derivatives (superoxide and hydroxyl radicals). Cells have developed a comprehensive array of antioxidant defences including enzymes to decompose free radicals and free radical scavengers to prevent free radical formation and limit their damaging effects…

The aetiology of pre-eclampsia is not fully understood but an impaired maternal immunoprotective response towards the trophoblast is considered to be an initial factor (Clark, 1994). A number of facts have led to the idea that immunological components may have a role to play in the development of pre-eclampsia. These include the following; the greater the exposure to semen (an allogenic antigen for women) the less likelihood that pregnancyinduced hypertension (PIH) will occur; pre-eclampsia is more likely to arise in women who change partners. Also, previous blood transfusions protect against pre-eclampsia. These observations suggest that there may be immunological abnormalities present in the development of pre-eclampsia…

Maternal immunological tolerance is necessary in the establishment and maintenance of a normal pregnancy. The fetus carries genetic material from the mother and the father so that fetal tissues and fetal cells crossing the placental barrier posses foreign antigenic properties for the maternal immune system. The apparent paradox that embryos are not rejected by the maternal immune system despite the presence of paternal major histocompatability complex (MHC) histocompatability antigens has been explained in mice using the Th1/Th2 model with pregnancy being associated with a Th2 response (Wegman et al., 1993). Human CD4 T helper lymphocytes can be subdivided into at least three distinct functional subsets on the basis of their cytokine profiles. One type of CD4+ lymphocyte, T helper 1 cells (Th1) produces IFNγ and IL-12, the Th2 subset produces IL-4 and IL-5, and the third, Th0, produces both Th1 and Th2 type cytokines. The Th1 cells promote the production of opsonising and complement fixing antibodies, macrophage activation and antibody-dependent cell cytotoxicity. Th2 cells provide optimal help for humoral immune responses including IgE isotype switching and mucosal immunity…

Cytokine production is known to play a major role in whether a pregnancy progresses satisfactorily to term or whether the pregnancy again ends in miscarriage. Many studies have examined events occurring in the peripheral circulation and found that peripheral blood cytokine levels differ significantly between women who miscarry compared to those who have a successful pregnancy. However, there are inherent differences that exist between peripheral and endometrial lymphocyte populations. This chapter aims to examine events occurring at the maternal fetal interface and determine whether or not this is similar to what occurs in the peripheral circulation…

The body has a multi-layered antioxidant system that copes with excessive production of reactive oxygen species (ROS). If the balance between ROS production and the protective mechanisms is shifted in favour of prooxidants, then excessive ROS results and this can be damaging. Damage from free radicals (oxidative stress) and lipid peroxidation has been involved in the pathophysiology of a variety of clinical conditions. Their role in preeclampsia is well documented. Although oxidative stress has also been implicated in pregnancy and in the aetiology of miscarriage (Simsek et al., 1998) the role of antioxidants in recurrent miscarriage is poorly understood…

Patients with autoimmune thyroid disease have T cells in their blood and within the thyroid gland that recognise specific thyroid molecules, thyroglobulin, thyroid peroxidase and the thyroid stimulating hormone (TSH) receptor. Some of these T cells are able to kill ‘self’ thyroid cells and activate B cells to secrete autoantibodies that bind to these same thyroid molecules (O'Connor and Davis, 1990). Antithyroid antibodies are found in apparently healthy populations and are found more frequently in women in their reproductive years (Geva et al., 1997). For more than 20 years the autoimmune system has been thought to have a role to play in miscarriage with lupus anticoagulant being associated with an increased abortion rate (Scott et al., 1987). In addition, women who were habitual aborters were shown to be positive for numerous antibodies (Cowchock et al., 1986). There is now considerable evidence to suggest a link between the presence of thyroid antibodies and pregnancy loss…

The following sections are included:

• Index