Elsevier

Placenta

Volume 29, Issue 7, July 2008, Pages 639-645
Placenta

Pathophysiology of Placenta Creta: The Role of Decidua and Extravillous Trophoblast

https://doi.org/10.1016/j.placenta.2008.04.008Get rights and content

Abstract

Placenta creta is associated with massive postpartum hemorrhage and commonly leads to emergency hysterectomy. While the exact pathogenesis of placenta creta is unknown, proposed hypotheses include a primary deficiency of decidua, abnormal maternal vascular remodeling, excessive trophoblastic invasion, or a combination thereof. To assess these changes in placenta creta, we retrospectively reviewed 49 cases of gravid hysterectomy, 38 with and 11 without the diagnosis of creta, gathered clinical data, and evaluated histopathology of extravillous trophoblast. Specifically, we evaluated maternal vessels for remodeling by endovascular trophoblast, as well as the morphology and depth of invasion of interstitial trophoblast at the implantation site. Compared to controls, cases with creta had decreased proportion of remodeled vessels, with many vessels displaying partial physiologic change. Cases with creta also demonstrated vascular remodeling deeper in the myometrium; however, vascular remodeling of large outer myometrial vessels was only demonstrated in increta and percreta cases, and was absent in both non-creta and accreta. As previously reported, interstitial trophoblast invaded the uterine wall to a significantly greater depth in placenta creta; however, there was no significant difference between creta subtypes. Finally, Ki-67 staining was rarely observed in extravillous trophoblast, except in the trophoblast columns of first trimester creta cases. We, therefore, conclude that the pathogenesis of placenta creta is multi-dimensional, involving increased, but incomplete trophoblast invasion in a background of absent decidua. We further propose that placenta increta and percreta are not due to a further invasion of extravillous trophoblast in the uterine wall, rather they likely arise secondary to dehiscence of a scar, leading to the presence of chorionic villi deep within the uterine wall, and thus give extravillous trophoblast greater access to the deep myometrium.

Introduction

Placenta creta is a severe pregnancy complication, associated with massive immediate postpartum hemorrhage, which often necessitates hysterectomy. It can be further subdivided into accreta, increta, and percreta based on the depth of placental villous tissue in the uterine wall [1]. Histologically, creta is characterized by the lack of intervening decidua and direct contact of villous tissue with the underlying myometrium [2]. In normal pregnancy, decidualized endometrial stroma is the site of placental separation from the uterine wall by the shearing action between the contracting myometrium and the non-contracting placenta. In placenta creta, the absence of decidua prevents separation, thus leading to a clinically adherent placenta and subsequent bleeding.

In addition to decidual deficiency, several studies have suggested excessive trophoblast invasion may contribute to the pathogenesis of placenta creta [3], [4], [5]. Normal implantation involves invasion of the uterine wall by two subgroups of extravillous trophoblast: the interstitial trophoblast invades through the endometrium and the superficial one-third of the myometrium, while the endovascular trophoblast invades and remodels the maternal spiral arterioles [2]. The latter process involves loss of the smooth muscle in the arterial wall, resulting in vessels with dilated lumina with a hyalinized wall containing endovascular trophoblast [2]. Previous studies have suggested various abnormalities in both trophoblastic subtypes, including both defective and excessively deep vascular remodeling [1], [2], [6], [7]. It is believed that in placenta creta, there is defective interaction between maternal tissues and migratory trophoblast in the early stages of placentation, coupled with the development of an abnormal uteroplacental circulation, resulting in deep trophoblast penetration into the uterus and thus adherence of the placenta [2], [6].

Some authors have suggested absent decidua to be the primary factor in placenta creta, and the etiology of excessive trophoblast invasion [8], [9]. Comparison has been made to tubal gestation, where absence of decidua is associated with deep invasion of trophoblast into adjacent vessels [2]. However, work of Ramsey and others in various primate species has shown a more complex, non-linear relationship between decidualization and trophoblast invasion [10], [11]. In addition, some authors have suggested that decidua is present at the start of gestation and atrophies as the pregnancy proceeds, although no supportive data was presented [6], [8]. While the lack of decidua remains etiologically unexplained, the strong association of placenta creta with a history of prior c-sections and endometrial curettage suggests a role for uterine scarring [1], [2], [6], [8], [9], [12].

Given the controversies and conflicting data regarding the role of decidual deficiency and trophoblast invasion in pathophysiology of creta, this study was undertaken to systematically review the histology of placenta creta and evaluate the extent of decidualization and trophoblast invasion in this disease, compared to a control group. Based on a comprehensive histologic analysis of gravid hysterectomy specimens from all three trimesters, we conclude that placenta creta is primarily a maternal disease rooted in decidual deficiency, at least partially due to uterine scarring, and with secondary defects in trophoblast invasion and function.

Section snippets

Tissue samples

Following IRB approval, cases of gravid hysterectomy were retrieved from surgical pathology files of the Women's and Perinatal Pathology Division, at Brigham and Women's Hospital, from 2002–2007. Only patients who had available clinical data and paraffin-embedded tissue specimens were included in this study. The cases consisted of 16 cases of accreta, 17 increta, and 5 percreta (total of 38 cases). Accreta was diagnosed when chorionic villi were implanted on the myometrium without intervening

Clinicopathologic features

There were 53 cases of gravid hysterectomy during the study period. Forty cases (75.4%) were histopathologically diagnosed as placenta creta. Four cases (two placenta creta and two non-creta) were excluded because of lack of information or unavailable paraffin blocks. The clinical data of the remaining 49 cases of gravid hysterectomy included in our study are presented in Table 1. Most cases were in the second and third trimester. Four cases of placenta creta were in the first trimester,

Discussion

Placenta creta is generally defined as implantation of anchoring villi on uterine myometrium without intervening decidua [13]. The reported incidence varies from 1 in 533–70,000 deliveries [14], [15], depending on differences in definition (clinical vs. confirmation by histology), study populations, as well as the study period. Several reports have noted the increasing incidence of creta over the past decades [13], [16], [17]. This finding may be explained by the increasing rates of c-sections.

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