Causes of recurrent miscarriage

	Causes and risk factors	Examples
Epidemiological factor	Increase maternal age
	Increase paternal age
	Increase number of previous successive miscarriage
Genetic factor	Parental chromosomal abnormalities	Parent with balanced Robertsonian translocation
	Embryo chromosomal abnormalities	Embryo with imbalanced Robertsonian translocation
Anatomical factor	Congenital uterine malformation	Arcuate uteri, septate uteri
	Cervical weakness / incompetence
Maternal health condition	Anti-phospholipid syndrome
	Obesity
	Endocrine disorders	Thyroid disorder
		Diabetes mellitus
		Polycystic ovarian syndrome
	Thrombophilia
Infection	Bacterial vaginosis

Robertsonian translocation is a type of chromosomal rearrangement caused by fusion of 2 particular chromosomes. A person with Robertsonian translocation may have either a balanced translocation or an unbalanced translocation. When the translocation is balanced, the person with it is called Robertsonian translocation carrier. As a carrier, they are normal and healthy, and many of them never discover about their unusual chromosome rearrangement. Meanwhile, unbalanced translocation will lead to either a baby with congenital malformation or even a not viable one.

About 2 – 5 % of couples with recurrent miscarriage, one of the partner carries a balanced Robertsonian translocation (Robertsonian translocation carrier). There are 4 possible outcomes when 1 of the parent is a Robertsonian translocation carrier : 1) A normal baby. 2) The baby is a carrier. 3) A baby with congenital malformation. 4)Pregnancy loss, miscarriage.

Robertsonian translocation

Women with uncontrolled diabetes mellitus in 1st trimester are at risk of miscarriage and fetal malformation. However, a woman with well-controlled diabetes mellitus is not at risk of recurrent miscarriage.

Same with diabetes mellitus , thyroid dysfunction, if treated and well controlled, it is not a risk factor for recurrent miscarriage.

Meanwhile, increased risk of miscarriage in women with PCOS is said to be related to insulin resistance, hyperinsulinemia (high insulin in blood) and hyperandrogenemia (high androgen in blood).

Arcuate uterus increases the risk of 2nd trimester miscarriage and preterm labor ,while septate uterus is more likely to cause miscarriage in the 1st trimester. It is said that this is due to uterine distortion in these congenital uterine anomalies, which make the uterine unable to provide adequate support for the pregnancy.

Classification of congenital uterine anomalies

 

Miscarriage – recurrent miscarriage

Miscarriage is defined as spontaneous loss of pregnancy before fetus reaches viability, which include all pregnancy losses from the time of conception until 24 weeks of gestation.**After 24 weeks of gestation, the term ‘stillbirth’ is used. 

Miscarriage is a common pregnancy complication. About 1 in 5 pregnancy ends with miscarriage. Usually, miscarriage is a complication that occurs by chance. A woman with 1^st time 1^st trimester miscarriage will be expected to have a normal following pregnancy just like any other normal lady. However, if a woman develops recurrent miscarriage or 1 or more 2^nd trimester miscarriage, the cause of the miscarriage should be investigated.

The causes and risk factors of recurrent miscarriage include: 1) Increase maternal age 2) Increase number of previous miscarriage 3)Obesity  4)Anti-phospholipid syndrome 5)Genetic abnormalities 6)Endocrine disorder 7)Infection 8)Thrombophilia 9)Anatomical abnormalities.

Advancing maternal age is associated with a decline in both number and quality of the remaining oocytes (eggs). Advanced paternal age has also been identified as a risk factor for miscarriage. The risk of miscarriage increases when a woman is 35 years old and above, and when a man is 40 years old and above. Meanwhile, for  women with history of successive pregnancy losses, the risk of further miscarriage increases with each successive pregnancy loss.

Anti-phospholipid syndrome is the most common treatable cause of recurrent miscarriage.It is a syndrome characterized by association between the presence of anti-phospholipid antibodies and pregnancy complications or vascular thrombosis. The pregnancy complications said may include 1 or more of the following: 1)3 or more consecutive miscarriage before 10 weeks gestation. 2)1 or more morphologically normal fetal losses after 10 weeks gestation. 3)1 or more preterm birth before 34^th weeks gestation due to placental disease.

Miscarriages caused by genetic problem can be either due to abnormality in the parents’ chromosome (parental chromosomal abnormality), or due to abnormality in the embryo chromosome itself (embryo chromosomal abnormality).

There is a number of maternal endocrine disorders which have been associated with increased risk for miscarriage. These include diabetes mellitus, thyroid disorder and polycystic ovarian syndrome. Obesity is also known as a risk factor for miscarriage.

Anatomical abnormalities of the female organ also can lead to recurrent miscarriage. These include congenital uterine malformation such as arcuate uteri and septate uteri, and cervical weakness. Cervical weakness or incompetence usually leads to 2^nd trimester miscarriage.

Other causes include infection and thrombophilia. Infection such as bacterial vaginosis usually leads to 2^nd trimester pregnancy losses and preterm delivery.  Meanwhile, thrombophilia, whether inherited or acquired, is said to be the possible cause of recurrent miscarriage and late pregnancy complication - with presumed mechanism being - thrombosis of utero-placental circulation.