Miscarriage is defined as pregnancy loss prior to 20-weeks gestation. The risk of miscarriage is largely related to the age of the woman: approximately 10 – 15% in the 20’s; 15 – 20% in the 30’s; up to 50% in the early – mid 40’s.

Recurrent miscarriage has traditionally been defined as ≥3 consecutive pregnancy losses prior to 20-weeks gestation. It occurs in 1% of couples. A cause can be identified in 50 – 66% of cases. Due to the distress recurrent miscarriage causes, the American Society of Reproductive Medicine advocates the investigation of couples after 2 losses.

Causes, Investigation and Management

An overview of the causes, investigation, and management of recurrent miscarriage is given below:

Genetic factors

  • In 2 – 5% of couples with recurrent miscarriage, one of the pair will carry an error in their chromosomes
  • For this reason, a Karyotype is performed
  • Should an error be found, Pre-implantation Genetic Diagnosis (PGD) may be recommended

Anatomical factors

  • In 15 – 25% of couples with recurrent miscarriage, the woman will have a uterine anomaly
  • Anomalies may be congenital (e.g. uterine septum) or acquired (e.g. fibroid)
  • For this reason, an assessment of the uterine cavity (Sonohystogram) is performed
  • Should an anomaly be found, surgical correction may be recommended

Endocrine factors

  • In 10 – 15% of couples with recurrent miscarriage, the women will have evidence of endocrine dysfunction
  • Endocrine dysfunction may include: diabetes, PCOS, hypo-/ hyperthyroidism, and elevated prolactin
  • For this reason, a complete endocrine profile is performed
  • Should endocrine dysfunction be found, a referral to an Endocrinologist may be recommended

Thrombotic factors (thrombophilias)

  • In 15 – 20% of couples with recurrent miscarriage, the woman will have evidence of prothrombotic (increased risk of clotting) tendencies
  • A prothrombotic state may be congenital (e.g. Factor V Leiden) or acquired (e.g. Anti Cardiolipin Antibodies)
  • There is evidence that acquired thrombophilias are associated with recurrent miscarriage; the evidence for congenital thrombophilias is conflicting
  • For this reason, a full thrombophilia screen is performed
  • Should a thrombophilia be found, a referral to a Haematologist may be recommended; treatment with the anticoagulant Heparin (Clexane) +/- Aspirin may be considered

Immunological factors

  • The role of immunological factors such as uterine Natural Killer cells (uNK cells) is debated in the literature
  • There is no conclusive evidence that elevated NK cells (detected via a blood test or endometrial biopsy) are associated with recurrent pregnancy loss
  • Furthermore, there is no conclusive evidence that proposed therapies such as Clexane, Prednisone, and Intralipid are effective
  • For this reason, testing for uNK cells will only take place after extensive counselling

Unexplained

Unfortunately, no obvious cause can be found in 34 – 50% of cases. The reassuring news is that the majority of couples have success with a subsequent pregnancy. Potential treatment options include:

Supportive care

There is evidence that regular review, checking of pregnancy hormone levels, and appropriately timed ultrasounds result in a positive outcome.

Progesterone supplementation

There is some evidence that progesterone supplementation has a role in women with unexplained recurrent miscarriage.

Pre-implantation Genetic Screening (PGS)

Finally, whilst debate exists in the literature regarding the role of PGS for recurrent miscarriage, undertaking IVF for the purposes of PGS has the following advantages:

  • Ensures that an embryo with a normal chromosomal complement is transferred
  • Unravels the interaction between the roles of the embryo and various implantation factors in miscarriage
  • It is likely, that if a woman continues to miscarry chromosomally normal embryos then an implantation factor becomes more likely