Evidence-Based Management of Recurrent Pregnancy Loss

Abstract

Up to 5% of women trying to conceive experience recurrent pregnancy loss (RPL), and incidence increases with maternal age. 1,2 The definition of RPL, or miscarriage, has recently changed from 3 or more consecutive miscarriages to 2 or more losses. Pregnancy loss is defined by the American College of Obstetricians and Gynecologists (ACOG) as "loss of a pregnancy before 20 weeks" of gestation, although the Royal College of Obstetricians and Gynaecologists defines it as "a spontaneous loss of pregnancy before the fetus reaches viability." Two or more miscarriages warrants consideration of a workup for the potential causes, which will help direct management of each case. Although RPL is common, there is great confusion as to the diagnostic tests and treatments supported by existing evidence. This has produced a significant gap between evidence-based and typical care. The purpose of this article is to address this gap by providing a summary of existing evidence regarding RPL and recommendations for appropriate evaluation. Etiology of RPLGenetic defects, particularly aneuploidies, are the most common cause of early pregnancy loss. Fifty percent of early pregnancy losses can be attributed to these genetic defects, which are more common in pregnancies with advanced maternal age. Disorders such as autoimmune phospholipid syndrome (aPLs) represent the most common autoimmune cause of RPL. Other etiologies such as endocrine disorders and uterine abnormalities make up 11% of cases of RPL. A large percentage of those with RPL have a cause that remains unknown. Of couples with unexplained RPL, 75% have a subsequent live birth, although this percentage varies with age (92% for a 20-year-old woman to 20% in women older than 40 years). 3 Advanced Maternal AgeThe most common risk factor for RPL is advanced maternal age (generally considered 35 years or older), which increases the risk for many other associated problems such as aneuploidies, maternal diabetes, and other endocrinopathies. Detection of genetic defects may be accomplished by noninvasive screening with cell-free fetal DNA starting at 10 weeks' gestation. This screening test is now offered to women who will be at least 35 years of age at the time of delivery. 4 As women in their reproductive years age, ovarian reserve decreases as a result of a smaller follicle pool. Although the decreased follicle pool and ovarian reserve are not directly associated with recurrent miscarriage, there is an association Learning Objectives: After participating in this CME activity, the obstetrician/gynecologist should be better able to: 1. Identify patients at increased risk for recurrent pregnancy loss. 2. Order and interpret diagnostic tests that are indicated on the basis of existing best evidence. 3. Initiate evidence-based treatment of recurrent pregnancy loss when indications are present.