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Recurrent miscarriage

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Recurrent miscarriage

Recurrent miscarriage or recurrent pregnancy loss (RPL) is the spontaneous loss of 2-3 pregnancies that is estimated to affect up to 5% of women. The exact number of pregnancy losses and gestational weeks used to define RPL differs among medical societies. In the majority of cases, the exact cause of pregnancy loss is unexplained despite genetic testing and a thorough evaluation. When a cause for RPL is identified, almost half are attributed to a chromosomal abnormality (ie. aneuploidy). RPL has been associated with several risk factors including parental and genetic factors (ie. advanced maternal age, chromosomal abnormalities, sperm DNA fragmentation), congenital and acquired anatomical conditions, lifestyle factors (ie. cigarette smoking, caffeine, alcohol, stress), endocrine disorders, thrombophila (clotting disorders), immunological factors, and infections. The American Society of Reproductive Medicine recommends a thorough evaluation after 2 consecutive pregnancy losses; however, this can differ from recommendations by other medical societies. RPL evaluation can be evaluated by numerous tests and imaging studies depending on the risk factors. These range from cytogenetic studies, blood tests for clotting disorders, hormone levels, diabetes screening, thyroid function tests, sperm analysis, antibody testing, and imaging studies. Treatment is typically tailored to the relevant risk factors and test findings. RPL can have a significant impact on the psychological well-being of couples and has been associated with higher levels of depression, anxiety, and stress. Therefore, it is recommended that appropriate screening and management (ie. pharmacologic, counseling services) be considered by medical providers.   

Pregnancy loss, also referred to as miscarriage or spontaneous abortion, occurs in up to 25% of pregnancies. Recurrent pregnancy loss occurs less frequently and it is estimated that 5% of women experience two consecutive pregnancy losses while only 1% experience three or more.

The cause of recurrent pregnancy loss is unknown in about 50% of cases. Risk factors that have been associated with RPL include parental and genetic factors (advanced maternal age, chromosomal abnormalities, sperm DNA fragmentation), anatomical conditions, lifestyle factors, endocrine disorders, thrombophila (bleeding disorders), immunological factors, and infections. Despite thorough evaluation for these risk factors, the exact cause for recurrent pregnancy loss is unknown in about 50% of cases.

Fifteen percent of women who have experienced three or more recurring miscarriages have some anatomical reason for the inability to complete the pregnancy. The structure of the uterus has an effect on the ability to carry a child to term. Anatomical differences are common and can be congenital or acquired.

While lifestyle factors have been associated with increased risk for miscarriage in general, and are usually not listed as specific causes for RPL. These include cigarette smoking, caffeine intake, alcohol use, BMI, and stress.

Women with hypothyroidism are at increased risk for pregnancy losses. Unrecognized or poorly treated diabetes mellitus leads to increased miscarriages. Women with polycystic ovary syndrome also have higher loss rates possibly related to hyperinsulinemia or excess androgens. Inadequate production of progesterone in the luteal phase may set the stage for RPL.

An important example is the possible increased risk of miscarriage in women with thrombophilia (propensity for blood clots). The most common problem is the factor V Leiden and prothrombin G20210A mutation. Some preliminary studies suggest that anticoagulant medication may improve the chances of carrying pregnancy to term but these studies need to be confirmed before they are adopted in clinical practice. Note that many women with thrombophilia go through one or more pregnancies with no difficulties, while others may have pregnancy complications. Thrombophilia may explain up to 49–65% of recurrent miscarriages.

A common feature of immune factors in causing recurrent pregnancy loss appears to be a decreased maternal immune tolerance towards the fetus.

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