Recurrent Pregnancy Loss

Recurrent pregnancy loss is a disease that is clearly distinguishable from infertility and is defined as two or more failed pregnancies. When the cause is unknown, any miscarriage needs to be carefully examined to determine if further testing is necessary. After three or more miscarriages, a thorough laboratory test is required. Although about 25% of all pregnancies end in miscarriage, less than 5% of women will experience two recurrent miscarriages, and only 1%, three or more. Couples who experience recurrent miscarriages can benefit from medical check-ups and psychological support.

Genetic/chromosomal causes: Chromosome analysis of the blood of parents identifies hereditary genetic causes in less than 5% of couples. Translocation (when part of a chromosome is linked to another chromosome) is the most common inherited chromosomal abnormality. Although the parent who has the translocation in genetic material is often normal, the fetus may receive too much or too little genetic material resulting usually in miscarriage. Couples with a translocation or other chromosomal abnormalities may benefit from pre-implantation genetic diagnosis in combination with in vitro fertilization.

In contrast to the unusual finding of an inherited genetic cause, many early miscarriages are due to the accidental occurrence of a chromosomal abnormality in the fetus. In fact, 60% or more of early miscarriages may be due to an accidental chromosomal abnormality, usually in missing or duplication of a chromosome.

Age: The risk of miscarriage increases as the woman gets older. After the age of 40, more than a third of all pregnancies end in miscarriage. Most of these embryos have an abnormal chromosome number.

Hormonal abnormalities: Progesterone, a hormone produced by the ovary after ovulation, is essential for a normal pregnancy. There is no agreement whether low progesterone level, a condition often referred to as luteal phase insufficiency, can cause recurrent miscarriages. Treatment may include ovulation induction, progesterone administration, or human chorionic gonadotropin (hCG) injections, but there is insufficient evidence for the effectiveness of these treatments.

Metabolic abnormalities: Inadequately controlled diabetes increases the risk of miscarriage. In women with diabetes, the outcome of pregnancy is better if the blood sugar is under control before conception. Women who are insulin resistant, such as obese women and many with polycystic ovary syndrome (PCOS), also have higher rates of miscarriage. There is not enough evidence yet to know whether drugs that improve insulin sensitivity reduce the risk of miscarriage in women with polycystic ovary syndrome.

Uterine abnormalities: Abnormalities in the uterine cavity can be found in about 10 to 15% of women with recurrent miscarriages. Screening diagnostic tests include hysterosalpingography (HSG), ultrasound, and hysteroscopy. Congenital abnormalities of the uterus include the double uterus, the uterine septum, and the uterus in which only one side is formed. Asherman syndrome (scar tissue in the uterine cavity), fibroids, and possibly polyps of the uterus are acquired abnormalities that can also cause recurrent miscarriages. Some of these conditions can be corrected surgically.

Antiphospholipid syndrome: Blood tests for anti-cardiolipin antibodies and lupus anticoagulants can detect women with antiphospholipid syndrome, a cause of 3 to 15% of miscarriages. A second blood test performed at least 6 weeks later confirms the diagnosis. In women with high levels of anti-phospholipid antibodies, the outcome of the pregnancy has improved with aspirin and heparin.

Thrombophilia: Certain inherited disorders that increase a woman's risk of developing severe thrombosis can also increase the risk of fetal death in the second half of pregnancy. However, there are no proven benefits for evaluation or treating women with thrombophilia and miscarriages in the first half of pregnancy.

Male factor: Evidence suggests that abnormal sperm DNA integrity may affect fetal development and may increase the risk of miscarriage. However, these data are still very preliminary and it is not known how often sperm abnormalities contribute to subsequent miscarriages.

Unexplained: There is no explanation for the 50 to 75% of couples with recurrent pregnancy losses.

Laboratory medical tests without proven benefit in the investigation of recurrent miscarriages include microbiological cultures for bacteria or viruses, tests for insulin resistance, antinuclear antibodies, anti-thyroid antibodies, maternal anti-paternal antibodies, antibodies against infectious agents, and embryotoxic agents.

Treatments without proven benefit include leukocyte (white blood cells) immunization and intravenous immunoglobulin therapy (IVIG).

Conclusion: A couple can be comforted by knowing that the next pregnancy is successful in 60 to 70% of people with unexplained recurrent miscarriages. A healthy lifestyle and folic acid supplement intake are recommended before attempting a new pregnancy. Quitting smoking, reducing alcohol and caffeine consumption, moderate exercise and weight control can all be particularly beneficial. Psychological support can also help deal with the sadness, anger, isolation, and fear that many people experience after repeated miscarriages.

Translation - Editing (in Greek): Vassilis Sideris

AMERICAN SOCIETY FOR REPRODUCTIVE MEDICINE, PATIENT’S FACT SHEET, Recurrent Pregnancy Loss, Revised 8/2008