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Repeated Miscarriages

Introduction

Miscarriages/Repeated Miscarriages are amongst one of the most shattering experiences, a woman can go through. Statistics have shown that 25% of all pregnancies result in miscarriages. Usually, it is seen that after having one miscarriage, a woman goes on to have a healthy pregnancy. But there are instances where a woman continues experiencing miscarriages for the second, third or multiple times. When a woman has two or three miscarriages in a row, they are considered having a problem of repeated miscarriages. This problem of repeated miscarriage is also often referred to as recurrent pregnancy loss.

It has been estimated that 1-2% of all the women suffer from the problem of repeated miscarriages. As the number of miscarriages increase, the chance of a miscarriage in the subsequent pregnancy increases After two miscarriages, a thorough medical examinations and tests become necessary.

Why Repeated Miscarriages Occur?

Causes of Repeated Miscarriages (RM):

RM can occur due to many factors, as discussed below. Unfortunately almost 50-60% of cases, all these factors are normal.

Genetic Causes

Approximately 2% to 4% of RM are due to genetic problems. The important genetic defect associated with RM is parental balanced structural chromosome rearrangement, most commonly balanced reciprocal or Robertsonian translocations. Additional structural abnormalities associated with RM include chromosomal inversions, insertions, and mosaicism. Single gene defects, such as those associated with cystic fibrosis or sickle cell anaemia, are seldom associated with RPL.

Anatomic Causes

Anatomic abnormalities account for 10% of cases of RM and are generally thought to cause miscarriage by interrupting the vasculature of the endometrium, prompting abnormal and inadequate placentation. Thus, those abnormalities that might interrupt the vascular supply of the endometrium are thought to be potential causes of RPL. These include congenital uterine anomalies, intrauterine adhesions, and uterine fibroids or polyps.

Cervical incompetence or weak cervix can result in repeated second trimester miscarriages. This can be congenital i.e. by birth or acquired due to trauma to cervix following deliveries or miscarriages.

Endocrine Causes

Luteal phase defect (LPD), polycystic ovarian syndrome (PCOS), diabetes mellitus, thyroid disease, and hyperprolactinemia are among the endocrinologic disorders implicated in approximately 17% to 20% of RPL.

Infections

Certain infections, including Listeria monocytogenes, Toxoplasma gondii, rubella, herpes simplex virus (HSV), measles, cytomegalovirus, and coxsackie viruses, are known or suspected as to play a role in isolated spontaneous pregnancy loss. However, infection is a very uncommon cause for RM, The proposed mechanisms for infectious causes of pregnancy loss include

Autoimmune Causes

Autoimmunity is characterised by formation of antibodies to one’s own antigens. It therefore follows that there may be abnormalities within these immunologic mechanisms that could lead to both sporadic and recurrent pregnancy loss.

One specific autoimmune disorder, Antiphospholipid Syndrome (APS) has been clearly linked with many poor obstetric outcomes, including RM, with a prevalence of 3% to 5% in the general population. APS is characterized by the presence of at least 1 clinical and 1 laboratory criterion:

Clinical

  • 1 or more confirmed episodes of vascular thrombosis
  • Pregnancy complications including either 3 or more consecutive pregnancy losses at less than 10 weeks of gestation, 1 or more fetal deaths at greater than 10 weeks of gestation, or at least 1 preterm birth (< 34 weeks) due to severe preeclampsia or placental insufficiency

Laboratory (repeated at least 2 times, more than 12 weeks apart)

  • Positive plasma levels of the anticardiolipin antibodies (IgG or IgM) at medium to high levels
  • Positive plasma levels of the lupus anticoagulant

Thrombophilia

Both inherited and combined inherited/acquired thrombophilias can cause RM. The most common of these are the factor V Leiden mutation, mutation in the promoter region of the prothrombin gene, and mutations in the gene encoding methylene tetrahydrofolate reductase (MTHFR). These common mutations are associated with mild thrombotic risks, leading to miscarriages

Unexplained Etiologies

In 50-60% of couples with RM, all the above factors are normal and are labelled as “Unexplained”. These cases are now considered to be due to “Alloimmune rejection of pregnancy by the mother’s immune system.