Section 5 -

Abnormalities of Implantation Phyllis C. Huettner, M.D.

Placenta Accreta, Increta and Percreta Case 6: Placenta Percreta Placenta accreta refers to a spectrum of findings with the common clinical feature of abnormal placental adherence and the common pathologic feature of absence of decidua between chorionic villi and myometrium. Accreta can be subdivided into placenta accreta vera where the chorionic villi abut against but do not invade the myometrium, placenta increta where the chorionic villi extend into the myometrium and placenta percreta where the uterus is perforated by chorionic villi that may then invade other structures such as the bladder. Placenta accreta may be focal, partial or complete. True incidence figures are very difficult to determine depending on whether clinical or a histopathologic criteria are used, the decades studied and the population studied. The reported incidence ranges from 1 in 540 to 1 in 93,000 deliveries. The incidence from a large series of accreta confirmed histologically in hysterectomy specimens is about 1 in 2500 deliveries. This represents a 10 fold increase in incidence over the last 10 years. Partial accreta is probably more common than complete and may be under reported. Placenta accreta is associated with certain well-established risk factors. The two most important of these are placenta previa and a history of prior Cesarean section. In one study, 89% of patients with accreta had previa and 73% had a prior Cesarean section. About one in 10 women with previa and one in 5 with both previa and prior Cesarean section develop accreta. In many cases, only that part of the placenta implanted over a prior Cesarean section scar is abnormally adherent underscoring the relationship between scar tissue and abnormal adherence. Other risk factors such as prior D&C and a history of uterine sepsis may also reflect uterine scarring as a result of trauma or infection. The need for manual removal of the placenta in a prior pregnancy may indicate a minor degree of abnormal adherence in the prior pregnancy and increases the risk of accreta in subsequent pregnancies. Implantation in non-fundic areas such as the cornu, over a submucosal fibroid or in a rudimentary uterine horn also increases the risk of accreta. The risk is also increased with increasing maternal age. Otherwise unexplained second-trimester elevated maternal serum alpha-fetoprotein and beta-hCG levels have been associated with increased incidence of placenta accreta. In about 10% to 20% of cases none of these risk factors are identified, prompting some to speculate that in some cases genetic factors may be responsible. Most cases of accreta are diagnosed during labor. Nevertheless, in women with risk factors prenatal ultrasound may be helpful. It has a sensitivity of about 65% and a specificity of about 40%. Color Doppler is even more sensitive and specific. A recent study in women with ultrasound results suggestive of accrete showed an improved sensitivity and specificity with pMRI. MRI was able to accurately determine the location of abnormal adherence and depth of invasion, factors that determine the likelihood of significant bleeding and may modify the surgical approach and degree of clinical readiness for complications. Clinical symptoms are usually not apparent and the diagnosis is often not suspected until after delivery of the baby when there is difficulty delivering the placenta. Placenta accreta is completely compatible with normal intrauterine growth and development although a recent study reports an increase in preterm delivery and delivery of small for gestational age infants with accreta. A minority of patients report severe abdominal pain and tenderness during pregnancy with no other explanation. All degrees of placenta accreta may be associated with severe postpartum hemorrhage. Over half of patients with accreta require transfusion; one in five requires 5 or more units. Often the only way to stop the bleeding is to perform an immediate hysterectomy. In large series of Cesarean and partum hysterectomy, accreta accounts for about a third of such hysterectomies. About 30% of patients experience antepartum bleeding but nearly all of these also have placenta previa. Uterine rupture complicates 13.8% of cases. Most ruptures occur in the second trimester prior to the onset of labor, almost always at the site of a previous scar. Uterine inversion is uncommon, complicating 2.1% of cases. It usually follows repeated attempts at manual extraction. Maternal mortality rate is 7% and is usually due to shock or DIC from extensive hemorrhage. Fetal death occurs in about 1% of cases and is usually related to uterine rupture and severe antepartum bleeding. Clinical management depends on the degree of hemorrhage. In one early study, the mortality rate in women treated by immediate hysterectomy was four times lower than that in woman initially treated by conservative management. More recently, selected cases have been treated by leaving all or part of the placenta in situ, with or without the addition of systemic methotrexate. The adherent placenta is either resorbed or passed later. Some patients have had subsequent normal pregnancies, including vaginal delivery, following such conservative management. No randomized clinical trials, cohort or case-control studies address the efficacy of this approach, however. The main pathologic finding in hysterectomy specimens performed for placenta accreta is the presence of chorionic villi adjacent to (accreta) or invasive into (increta) or through (percreta) myometrium. No decidual layer is present between chorionic villi and myometrium although there may be a layer of intervening connective tissue which contains scattered decidual cells. Intermediate trophoblast may be seen between villi and myometrium and may be difficult to differentiate from decidua on H&E sections. Trophoblast is cytokeratin positive and individual cells are enveloped by reticulin in contrast to decidual cells which are cytokeratin negative without surrounding reticulin. There is no evidence of hyperplasia of trophoblast in this disorder. Villous morphology is normal for gestational age. Myometrial fibers adjacent to villi may be degenerative or hyalinized. There may be increased amounts of connective tissue and acute and chronic inflammatory cells between myocytes. It is often difficult for the pathologist to make a diagnosis of placenta accreta. The placenta and even the uterus, when it is received, are often quite disrupted due to multiple attempts at manual removal. Thorough sampling of the basal plate of the placenta and the likely implantation site in the uterus, concentrating on the area of prior C-section scar, may reveal villi adjacent to myometrium without intervening decidua. The inability to document this histologically does not, of course, exclude a diagnosis of accreta. Conversely, at least one study has shown that careful sampling of the basal plate may reveal mild cases of placenta accreta that were not clinically suspected, which may have implications for future gestations. En face sections of the basal plate or sections from the junction between intact and macroscopically disrupted areas have the highest yield for myometrial fibers. The pathogenesis of this condition appears to relate to an abnormality of the endometrium such that insufficient decidual tissue forms. Implantation in non-fundic or scarred areas of the uterus or in areas of thinned or inflamed endometrium, such as over a submucous fibroid, represent such areas of abnormal endometrium. In a recent study, Sherer et al observed increased placental basal plate myometrial fibers in cases with preterm delivery and decreased placental weight often adjacent to abnormal basal plate vessels. They have suggested that early hypoxia may increase trophoblast invasion resulting in myometrium adherent to the basal plate. How this finding relates to the similar morphologic findings in placenta accreta is still unclear and has been questioned by others. Abnormalities of Placental Shape The placenta is usually a round to oval-shaped organ in which the umbilical cord inserts slightly off to one side of center. One of the most common abnormalities of shape is the presence of an accessory or succenturiate lobe. These are usually single but may be multiple and are found in about 3 to 5% of placentas. The accessory lobe may be separated from the main placenta by a thin amount of villous tissue or by fetal membranes devoid of underlying villi. Usually the umbilical cord inserts into the main body of the placenta and the succenturiate lobe is supplied by branches of the umbilical vessels that run, unprotected, in the connecting membranes. Succenturiate lobes are usually without clinical consequence but may be retained in utero where they can cause postpartum bleeding and infection or present as placenta previa. Uncommonly, the unprotected vessels between the main placenta and the succenturiate lobe are torn, resulting in fetal hemorrhage, or undergo thrombosis. The pathogenesis of this anomaly is unknown but theories include superficial implantation of the fertilized ovum which then adheres to both uterine walls, implantation into the lateral or apical sulcus, and failure of villous atrophy of a focal area of chorion laeve. In the bilobate placenta (also called bipartite or placenta duplex) there are two lobes of approximately equal size separated by fetal membranes or a thin bridge of chorionic tissue. The umbilical cord usually inserts between the two lobes. The incidence is as high as 4.2% in one study although in most studies it is much less common. Fujukura et al noted a significant association between bilobate placenta and multiparity, advanced maternal age, and a history of infertility. Women with bilobate placentas had significantly more first trimester bleeding, placenta previa and required manual placental extraction twice as often as women without bilobate placentas. There is no increased fetal morbidity or mortality with this condition. Placenta membranacea, also known as placenta diffuse, is a common form of placentation in animals but is very rare in humans where it is seen in about 1 in 20,000 to 1 in 40,000 deliveries. In this condition the differentiation into chorion frondosum and chorion laeve, which usually occurs between the 8th and 10th week, does not take place and all and most of the membranes are covered by chorionic villi. There may be an area of increased thickness of chorionic villi, resembling the placental disc, into which the umbilical cord inserts. Symptoms include recurrent bleeding in the late first and early second trimester probably due to villous tissue near the os. Most cases are associated with preterm delivery and fetal mortality, but Ahmed and Gilbert-Barnes have recently reported cases with no associated bleeding and one with a normal term delivery. Circummarginate and Circumvallate Placenta (Extrachorial Placenta) In extrachorial placentation the junction between the chorionic membranes and the chorionic plate of the placenta occurs not at the margin of the placenta, as is the usual situation, but at some distance from it so that there is placenta uncovered by membranes extending beyond the chorionic plate (hence extrachorial). In circummarginate placenta this junction forms a thin rim of fibrin and degenerate material where the fetal vessels of the chorionic plate terminate. In circumvallate placenta a thicker rim with a fold toward the center of the placenta is seen, histologic sections of which show avascular chorionic membrane, decidual tissue, villi, often with hyalinization, and sometimes fibrin and blood. Circummarginate and circumvallate placentation may be partial or complete. Some placentas show a combination of circummarginate and circumvallate features. Incidence figures vary widely probably depending on whether partial or complete cases are included. In one study of 3000 consecutive placentas 13.7% were partial circummarginate, 3.8% were total circummarginate, 4.5% were partial circumvallate and 2.4% were total circumvallate. Most studies show an increased incidence of all types of extrachorial placentation with increased parity. The clinical significance of extrachorial placentation is controversial. Most studies have found no clinical significance to circummarginate placentation. Total circumvallate placentation has been associated with recurrent antepartum bleeding, preterm labor and delivery, fetal hypoxia, post partum hemorrhage and low birth weight infants in some studies. It is thought by some that repeated episodes of bleeding into the decidua at the margin of the disc (chronic abruption) is responsible for circumvallation and that this chronic bleeding is associated with the adverse outcomes listed above. Diffuse chorioamniotic hemosiderosis is highly correlated with circumvallation (see membrane section). Circumvallation may recur in successive pregnancies. References: Placenta Accreta: ACOG Committee Opinion No. 266. Placenta Accreta. Obstet Gynecol 2002; 99:169-170. Aggarwal P et al. Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta. Hum Hered 2001; 51:114-116. Armstrong CA et al . Is placenta accrete catching up with us? Aust NZ J Obstet Gynceol 2004;44:210-3. Fox H. Placenta accreta, 1945-1969. Obstet Gynecol Survey 1972; 27:475-490. Gielchinsky Y et al. Placenta accreta-summary of 10 years: a survey of 310 cases. Placenta 2002;23: 210-214. Gielchinshky Y et al. Perinatal outcome of pregnancies complicated by placenta accrete. Obstet Gynecol 2004;104:527-30. Hung T-H et al. Risk factors for placenta accreta. Obstet Gynecol 1999;93:545-50. Iyasu S et al . 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