First and Second Trimester Pregnancy Loss

Pathologic exa mination o f t he p roducts o f em bryos a nd fetuses, both from spontaneous abortions (SAbs) and terminations of pregnancy, has become increasingly important. While s uch exa mination wa s o nce p erformed p rimarily for t he p urpose o f f urthering s cientiἀc un derstanding o f prenatal human development, the practical medical applications of this knowledge have become clear and now form an in tegral p art o f t he m edical a ssessment a nd m anagement of fertility i ssues (1–5). As an understanding of t he factors in volved in s uccessful p regnancies h as de veloped and as patient demand for information has increased, the role of pathologic examination has grown. Increased use of assisted fertilization techniques has heightened the interest of physicians and patients alike in understanding why pregnancies fa il. This c hapter w ill address t he exa mination o f disorders encountered in those pregnancies that end spontaneously in the ἀrst and second trimesters of gestation; the pathology of fetuses delivered after pregnancy termination after prenatal ultrasound diagnosis is beyond the scope of this chapter. It is recognized that many conceptions do not end in live births b ut, ra ther, t hat t here i s a hig h ra te o f s pontaneous loss, especially early in gestation. It is estimated that 10% to 20% of recognized pregnancies end as SAbs, with most losses occurring in the ἀrst trimester (ἀrst 12 to 14 weeks of gestation). With t he dem onstration o f f etal c ardiac ac tivity, t he miscarriage rate drops to approximately 3% to 12% (6). In a study of women with a normal prenatal visit at 6 to 11 weeks of gestational age (GA), the risk of subsequent SAb was 1.6% or less, considerably lower than for pregnancies overall (7). After the ἀrst trimester, approximately 1% to 2% of pregnancies a re s pontaneously a borted (8). The in cidence o f s tillbirth at term gestation is in the order of 0.1% to 0.5%. These loss ra tes t hat p ersist t hroughout g estation, t ogether w ith changing or c hanged s ocietal approaches a nd exp ectations of pregnancy such as de laying childbearing until l ater in a woman’s r eproductive lif e a nd in creased acces s t o a ssisted reproduction m ethods, h ave le d t o a n in tense in terest in understanding the cause of pregnancy loss and the implications for future reproductive success. GA refers to the number of weeks since the last menstrual period (equivalent to menstrual dates), while developmental age (DA) or conceptual age (CA) r efers to the age as determined from the time of fertilization, generally considered as a pproximately 2 weeks a fter t he l ast m enstrual p eriod. Embryos are assessed by developmental features that correlate with age, usually given as DA. Thus, in a n ormal gestation, GA is DA plus 2 weeks. The ἀrst trimester of pregnancy is the period of implantation and embryogenesis, with the completion of embryogenesis by 8 weeks of DA (10 weeks of GA). Upon completion of embryogenesis with development of all organ systems, the conceptus i s referred to as a f etus. Deἀnitions of fetus and infant vary with locale; in C anada, a f etus is considered an infant once it has reached the GA of 20 weeks or is liveborn at any GA. In the United States, by contrast, the living intrauterine conceptus is referred to as a fetus until the time of live birth. Stillbirth is deἀned as delivery of a deceased conceptus at or after 20 weeks of GA.