Placenta Accreta Spectrum

Pathogenesis

In 1937, Irving and Hertig published a cohort of 18 cases, which they described clinically as “the abnormal adherence of the afterbirth in whole or in parts to the underlying uterine wall” and histologically as “the complete or partial absence of the decidua basalis,” signs that are still used today by clinicians and pathologists. They defined all their cases as adherenta where the villi were attached to the surface of the myometrium without invading it. They hypothesized that the lack of a plane of cleavage between the placental basal plate and the uterine wall leads to major hemorrhage if an attempt is made to forcibly remove villous tissue attached superficially to the myometrium. Their series did not include a single case of invasive PAS; thus their clinical and pathologic descriptions were limited to abnormally adherent accreta.

Several concepts have been proposed to explain the abnormal placentation in PAS, including a primary defect of trophoblast function, a secondary basalis defect due to a failure of normal decidualization, and more recently, abnormal vascularization and tissue oxygenation of an area of scar. Unlike the epithelial layers of the endometrium and uterine peritoneum, which heal by regeneration and recolonization of the scar area, the myometrium does not heal by regenerating muscle fibers, but by forming “foreign” substances, including collagen. The resulting fibrous tissue is weaker, less elastic, and more prone to injury than intact muscle. Myofiber disarray, tissue edema, inflammation, and elastosis have all been observed in uterine wound healing after surgery. Different surgical techniques such as single-layer versus double-layer closure of the myometrium, locked versus unlocked single-layer closure, or the suture material used for the closure may influence the healing process and the risks of subsequent uterine rupture, but data regarding the influence of these factors on the risk of PAS in subsequent pregnancies are sparse.

Large cesarean scar defects may lead to scar dehiscence with advancing gestation ( Fig. 21.3 and 21.4 ) and could even explain exceptionally rare cases of PAS leading to uterine rupture in the first half of pregnancy. Although this is an extremely rare complication of abnormal placentation, the mechanism of uterine rupture due to invasive PAS is likely similar to that of a tubal rupture in ectopic placentation. Scar dehiscence in the third trimester can also lead to false-positive diagnosis of invasive PAS when the lower edge of a low-lying placenta becomes visible under the uterine serosa at laparotomy. There is increasing evidence that some pregnancies diagnosed as “cesarean scar” pregnancies are a precursor to PAS, although epidemiologic evidence remains limited to a few retrospective cohort studies.

PAS is not exclusively a consequence of a prior uterine surgical scar, and extensive non-surgical endometrial damage such as that related to endometritis can lead to endometrial fibrosis and atrophy with secondary poor decidualization and development of PAS in a subsequent pregnancy. This may explain why before the advent of antibiotics a prior manual removal of the placenta with or without a uterine curettage was the main factor associated with PAS in subsequent pregnancies. Although fragments of myometrium are found in the products of conception in about one-third of specimens from uterine curettage for miscarriage, the observation that these procedures are not a major risk for subsequent PAS suggests that the trauma to the myometrium and endometrium is often relatively limited from a curettage procedure compared to that from a CD.

Histologic findings reveal that large and deep myometrial defects are often associated with the absence of re-epithelialization of the scar area . Leukocyte recruitment to the endometrium is observed during the normal secretory phase and has been reported to be increased following a CD. A prior CD increases not only the risk of PAS in subsequent pregnancies but also the risk of placenta previa, suggesting a tropism of the blastocyst for the scar area. Uterine artery resistance is increased, and the volume of uterine blood flow as a fraction of maternal cardiac output is decreased in women with a previous CD compared to women with a previous vaginal birth. Overall, these data suggest a possible relationship between a poorly vascularized uterine scar area and an increase in resistance to blood flow in the uterine circulation. This supports the concept of a primary deciduo-myometrium defect in PAS, in which the myometrium and its vasculature below the junctional zone are exposed to the migrating extra-villous trophoblast and villous tissue ( Fig. 21.5 ). The loss of the normal plane of cleavage and the attachment of villi into the wall of radial and arcuate arteries may explain the clinical symptoms of invasive placentation ( Table 21.1 ).

These data indicate that significant damage to the uterine wall is associated with a secondary failure of decidualization in the area of the scar, which has an impact on both implantation and placentation. The decidual defect may have an adverse effect on early implantation by creating conditions for preferential attachment of the blastocyst to scar tissue and facilitating abnormally deep invasion of the villous tissue into the uterine wall and beyond.

Epidemiology

When Irving and Hertig published their cohort in 1937, only one of their 18 cases had been previously delivered by cesarean section. By 1966, when Luke et al. published their series of PAS, 9 of their 21 cases had a previous history of CD. With the rapid increase in CD rates over the last two decades, a prior CD has become the main risk factor for the development of PAS in subsequent pregnancies, while other factors are now responsible for a relatively small proportion of accreta placentation. The risk of PAS increases with the number of prior CDs. A recent systematic review and meta-analysis reported summary odds ratio (OR) of 2.95 (95% CI, 1.32 to 6.60) for placenta accreta after a CD. Due to high interstudy heterogeneity in methodology and lack of availability of some data, the study could not perform further analysis to stratify risk by the number of prior CDs. In other studies, when the risk of PAS has been stratified by the number of previous CDs, the ORs for PAS disorders increased from 8.6 (95% CI, 3.5 to 21.1) after one prior CD to 17.4 (95% CI, 9.0 to 31.4) after two previous CDs, and to 55.9 (95% CI, 25.0 to 110.3) after three or more prior CDs. A multicenter study of 30,132 women who underwent non-labored CD in 19 academic hospitals in the United States between 1999 and 2002 found that 143 had PAS disorders and that the absolute risk increased from 0.24% after one prior CD to 6.74% after six or more previous CDs. The recent Nordic Obstetric Surveillance Study (NOSS) found that the risk of invasive PAS (after exclusion of cases of adherent PAS and/or simple placental retention) increased seven-fold after one prior CD.