Repeated Miscarriages

Miscarriages are amongst one of the most shattering experiences, a woman can go through. Statistics have shown that 20% 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.

Only about 1% of women tend to have miscarriages in a row. After three miscarriages, a thorough medical examinations and tests become necessary.

Causes of Miscarriages

Genetic Etiologies

Approximately 2% to 4% of RPL is associated with a parental balanced structural chromosome rearrangement, most commonly balanced reciprocal or Robertsonian translocations. Additional structural abnormalities associated with RPL 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 Etiologies

Anatomic abnormalities account for 10% to 15% of cases of RPL 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 Etiologies

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.

Infectious Etiologies

Certain infections, including Listeria monocytogenes, Toxoplasma gondii, rubella, herpes simplex virus (HSV), measles, cytomegalovirus, and coxsackieviruses, are known or suspected as to play a role in sporadic spontaneous pregnancy loss. However, the role of infectious agents in recurrent loss is less clear, with a proposed incidence of 0.5%2 to 5%. The proposed mechanisms for infectious causes of pregnancy loss include:

(1) direct infection of the uterus, fetus, or placenta,
(2) placental insufficiency,
(3) chronic endometritis or endocervicitis,
(4) amnionitis, or
(5) infected intrauterine device.

Immunologic Etiologies

Since a fetus is not genetically identical to its mother, it is reasonable to infer that there are immunologic events that must occur to allow the mother to carry the fetus throughout gestation without rejection. In fact, there have been at least 10 such mechanisms proposed. 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, APS, requires particular attention, as it has been clearly linked with many poor obstetric outcomes, including RPL. The discussion of APS could also appear within the context of thrombophilias, given that it is the most frequently acquired risk factor for thrombophilia, 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 (venous, arterial, or small vessel)
  • 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
Thrombotic Etiologies

Both inherited and combined inherited/acquired thrombophilias are common, with more than 15% of the white population carrying an inherited thrombophilic mutation. 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, and it remains controversial whether homozygous MTHFR mutations are associated with vascular disease at all.

Unexplained Etiologies

While all known and potential causes for RPL are clarified, almost half of patients still persist without a definitive diagnosis.