Morbidly adherent placenta: the need for standardization

Morbidly adherent placenta (MAP) occurs when the placenta fails to detach from the uterine wall due to abnormal implantation at the basal plate. This often leads to massive obstetric hemorrhage and sequelae such as need for blood transfusion, multiorgan failure, need for morbid hysterectomy and even death1. Owing to the relative rarity of the condition, few high-quality data are available regarding optimal management. However, MAP is associated with considerable morbidity and is increasing in frequency2, 3, particularly in developed nations2-7, likely due to a dramatic and persistent increase in the rate of Cesarean delivery2-8. Determination of optimal management has been further hampered by a lack of standard nomenclature. Some definitions are clinical, others are based on imaging, while still others are based on histopathology, and there is considerable variation in the definitions used among countries, regions, hospitals and even clinicians. Cases of MAP managed conservatively (without hysterectomy) are hard to define since there is no specimen to evaluate histologically. Consequently, it is difficult to compare results of studies and hence to improve care for affected women. This problem is highlighted by studies on the conservative management of MAP. Excellent outcomes have been reported after hysterotomy, with the placenta left in situ, with partial removal of the placenta or with removal of the placenta with additional hemostatic suturing of the placental bed. However, none of these reported cases had invasive placentation confirmed based on histological examination. Thus, it is difficult to counsel women regarding the true risks of conservative management of MAP. Many of these women had fewer traditional risk factors for MAP (such as multiple prior Cesarean sections) than have been reported in other series. Accordingly, their outcomes may not be applicable to women with multiple prior Cesarean sections and placenta previa. Accurate prenatal diagnosis is critical to reduce the risk of maternal morbidity and mortality. Indeed, several studies have reported that antenatal diagnosis of MAP leads to a reduction of blood loss and other complications9-11. In part, this is due to planned Cesarean hysterectomy, with delivery of the infant through a fundal hysterotomy which avoids the placenta. In addition, it allows for planned delivery under optimal circumstances in a center of excellence with surgeons skilled in the delivery of pregnancies with MAP12. Unfortunately, the ability to diagnose MAP antenatally is imperfect, partly due to a lack of uniform nomenclature and partly due to significant overlap of the sonographic appearance of MAP with that of normally implanted placentae. There are numerous reports on prenatal diagnosis of invasive placentation using ultrasound13. In fact, relatively high sensitivities and specificities have been reported, albeit in high-risk cases and with full knowledge of clinical risk factors. Unfortunately, however, there is little consistency in the terminology used to describe the ultrasound features, which makes it difficult to compare studies of sonographically diagnosed MAP. There are also substantial clinical implications, since failure to diagnose MAP may lead to avoidable morbidity, while a false-positive diagnosis may result in unnecessary hysterectomy and loss of fertility. Clearly, there is a need for standardized nomenclature regarding the diagnosis, treatment and research of MAP. Several main sonographic features of invasive placentation have been described13, 14. (1) Direct visualization of placental tissue beyond the uterine cavity, such as a bulging mass in the urinary bladder. Although visualization of the placenta in the bladder cavity is strong evidence of abnormal placental invasion, this is a rare finding. Consequently, the sensitivity is low but specificity is high. Overall, the prevalence of this sign in cases of confirmed invasive placentation is very low. (2) Abnormalities of the placental–uterine interface. Using grayscale ultrasound, loss of the normal hypoechoic retroplacental space has been described as a sign of MAP. This feature is, however, operator- and angle-dependent, varies between anterior and posterior placenta and is associated with a high false-positive rate. (3) Reduced lower-segment myometrial thickness. The myometrial thickness in the lower segment is measurable to millimeters. A study in 30 women with previous Cesarean delivery, using both transabdominal (TAS) and transvaginal (TVS) sonography between 36 and 39 weeks of gestation, reported the thickness of the entire lower uterine segment to be 3.6–19.2 mm at TAS and 1.0–9.7 mm at TVS, with 95% limits of agreement of 3.5 mm and 0.8 mm, respectively. This metric was poorly reproducible and subject to considerable variation15. The sign has been described in many cases without invasive placentation, and its observed specificity is low16. (4) Abnormal color Doppler findings. Using color Doppler ultrasound, increased vascularity of the lower segment–urinary bladder interface has been described (Table 1). This is subjective, since currently there are no quantitative indicators to measure such increased vascularity; rather, there is the appearance of increased vascularity compared with that of normal controls. The location of the placenta in the lower uterine segment alone is sufficient to increase the vascularity in comparison to cases with a fundal placenta and, in pregnancies without MAP in women with prior Cesarean delivery, increased vascularity and scarring is often seen in the lower segment–urinary bladder interface. Indeed, ‘increased’ vascularity can be made to appear by changing the sensitivity of the ultrasound machine even in cases in which the placenta is not implanted in the lower uterine segment (Figure 1). In almost all publications involving placenta accreta, only women with known risk factors, such as low anterior placenta and previous Cesarean delivery, were examined. Therefore, selection bias may explain the ‘increased’ vascularity at the lower segment–urinary bladder interface. Often, it remains undetermined whether such ‘increased’ vascularity is a result of abnormal invasion or simply low-anterior placental location, and how this may be measured objectively requires clarification. Using offline analysis of volumes obtained with three-dimensional (3D) power Doppler ultrasound, Collins et al.17 showed a significantly increased area of vascular confluence in the maternal–fetal interface of the placenta in women with MAP as compared with controls. This could be helpful to reduce subjectivity in the reporting of increased vascularity associated with MAP. However, this technique is not readily available to clinicians and independent validation is needed before it can be used clinically. (5) Abnormal placental echostructure. Presence of placental lacunae was one of the first signs to be associated with MAP14, 18, 19. The pathophysiology is unclear, but may be due to placental tissue alterations resulting from long-term exposure to pulsatile flow. The content of the lacunae has been described variably as having low-velocity flow20, turbulent flow21, diffuse or focal flow22-24 or turbulent high-velocity flow25 (Table 2). ‘Abnormal’ and ‘confluent’ vessels have been described with invasive placentation, but no definition is available for the normal range of appearances. Furthermore, location and size of placental lacunae have not been defined clearly in relation to the prediction of MAP. (6) Parametrial invasion. Many series describe abnormal placental invasion anteriorly, presumably through a previous uterine scar. Lateral (parametrial) invasion of placental tissue has been demonstrated on magnetic resonance imaging (MRI)26. Insufficient healing of the uterine incision extending into the lateral wall, and implantation with subsequent invasive placentation extending into the parametrium, is a plausible explanation for this phenomenon. The frequency of parametrial invasion was 18% (62/342) of all cases of invasive placentation in one series26. There are two main theoretical approaches to the definitive ascertainment of MAP. One is histopathological confirmation and the other is based on surgical findings. Both are problematic for different reasons. Most cases of MAP belong to the placenta accreta spectrum, representing different grades of morbid placental attachment secondary to invasion of placental tissue deep into the myometrium beyond the normal uteroplacental interface. Placenta accreta is defined histologically as placental attachment to the myometrium without intervening decidua. Deep myometrial invasion is termed placenta increta and invasion through the myometrium into the serosa and beyond, even into surrounding structures such as the bladder, is termed placenta percreta. However, the term ‘placenta accreta spectrum’ is also often used in cases of clinically apparent MAP even if they have not yet been confirmed histologically. Placenta accreta is often defined simplistically as invasion of the myometrium with placental villi in contact with myometrial tissue. However, the main histological feature is the absence of normal decidua at the basal plate, and the detection of such findings is dependent on the mode of placental delivery and sampling issues. In one study, microscopic foci of myometrial tissue adherent to the basal plate with deficient intervening decidua, consistent with a mild or focal form of placenta accreta, were described in 36 placentae, of which only four had a clinical diagnosis of placenta accreta and none required hysterectomy27. It was concluded that mild cases of placenta accreta are frequently associated with previous uterine operations and multiparity, and are suspected clinically only infrequently. Similar findings were also reported in 44 of 457 (9.6%) preterm (birth < 32 weeks) placentae, with basal plate myometrial fibers present28. In another study of 90 consecutive singleton placentae, basal plate myometrial fibers were seen in 27 (30%)29; only nine of these had clinical features suggestive of placenta accreta, such as postpartum hemorrhage, delayed third stage of labor, retained placenta or need for manual removal. The high frequency of myometrial fibers was attributed to extensive sampling and it was suggested that myometrial fibers in the placental basal plate can confirm, but do not necessarily indicate, clinical placenta accreta. Conversely, conservative surgery may leave residual adherent parts of the placenta in situ, rendering histopathological confirmation impossible. Moreover, the pathologist is more likely to seek invasive placentation if extirpative surgery has been performed, whereas features of MAP may be missed if the pathologist assesses only a small number of routine placental sections. Furthermore, practice and expertise among pathologists varies considerably and there is no ‘standard’ approach for assessment and diagnosis of MAP. It is now generally agreed that, histologically, invasive placentation is characterized not only by proximity of villi and myometrium but also by histological lack of decidua between chorionic villi and myometrium, often with only fibrin intervening. We are not aware of any studies which have examined the effects of sampling on false-negative diagnosis, but hypothesize that insufficient sampling may lead to positive cases being histopathologically unproven. There are no objective criteria for intraoperative diagnosis of MAP. A diagnosis may be made when placental tissue is seen at the site of the surgical scar on direct visualization25, i.e. when the appearance of the scar resembles the fetal, rather than the maternal, surface of the placenta. However, it is not always easy to tell where the placenta ends and the myometrium begins. A vascular lower segment in a case of anterior placenta previa may well be indistinguishable from ‘placenta in the scar’. A diagnosis of MAP is also made when the placenta is adherent to the uterus and does not detach easily; however, again, this is subjective, with no clear distinction between MAP and ‘retained placenta’ in many cases. The ultimate aim in clinical diagnosis is prediction of major morbidity, regardless of whether invasive placentation is confirmed on histopathology or at surgery. Several risk factors for invasive placentation have been described. There is accumulating evidence to suggest that a Cesarean scar pregnancy detected in the first trimester is a precursor of MAP30-33, with a high proportion of these pregnancies resulting in MAP in the absence of intervention34-36. However, there is lack of agreement regarding the most appropriate diagnostic criteria for Cesarean scar pregnancy37. Furthermore, progression to MAP is not inevitable, as uncomplicated pregnancy and delivery has been reported following conservative management of Cesarean scar pregnancy37. In the second half of pregnancy, the most common and clinically important risk factor is the combination of placenta previa and previous lower-segment Cesarean delivery. Previous uterine surgery, such as myomectomy, curettage or endometrial resection/ablation, also increases the risk. While it is often difficult to know the exact site of previous injury, prenatal diagnosis of fundal placenta accreta has been described. In such cases, in which the placenta is not located in the anterior lower uterine wall, it is possible to deliver the infant without disturbing the placenta and to deal with it later. Hemostasis is likely to be easier and parametrial structures are not directly at risk. In a series of 187 women with placenta previa and previous uterine surgery, 46 (24.6%) had previous myomectomy and 23 (12.3%) had prior curettage, but none had confirmed MAP25. The greatest likelihood of MAP seems to be in women with presence of placenta in the anterior lower segment with previous lower-segment scar. It is unclear if women should be examined with empty, partly-filled or full urinary bladder, and whether TAS or TVS should be used. Prospective studies should be directed at collecting data using both modalities and with and without bladder filling in all cases, as well as assessing possible parametrial extension on ultrasound. The most appropriate gestational age at which assessment should be performed also needs clarification. The literature on MRI in the antenatal detection of MAP is biased because MRI is not a screening method. Moreover, the technique can only be as good as the individuals interpreting the images. It has been suggested that MRI is particularly valuable for investigation of parametrial invasion26. However, parametrial invasion is rarely reported. With the reported diagnostic performance of ultrasound being so good, with high sensitivity and specificity, it is debatable whether MRI can add substantially to this. Use of safe contrasts may improve the diagnostic performance of MRI in the future; in Europe38, the USA39 and Canada40, the use of contrasts in pregnancy is deemed acceptable when the benefits clearly outweigh the possible risks. Agreement as to what constitutes clinically significant invasive placentation is required. For it to be termed MAP, either the placenta should be anterior and low-lying (placental edge to internal os distance ≤ 2 cm) or there should be complete posterior placenta previa with anterior extension. In cases in which a fundal incision is made, the placenta should not detach spontaneously after delivery of the baby. Part of the placenta should remain attached to the uterine wall even if the rest of the placenta can be peeled off. Protocols for sampling have been published41, 42 and include between two and four full-thickness ‘random’ sections, each of which should have a variable amount of basal/maternal material, including decidua and/or myometrium. As described above, the presence of histopathological features without complications such as bleeding is of little clinical significance. Formal blinded assessment by histopathologists to ascertain the degree of interobserver agreement is required, with comparison to an agreed clinicopathological gold standard, for the diagnosis of clinically relevant MAP. Consensus is required regarding the definition of clinical and imaging features, such as ‘echo-poor areas’, and regarding lacunae, including their number and location, as distinguished from other ultrasonographic features such as ‘lakes’ or ‘fall-out areas’. Doppler interrogation of the contents of lacunae and documentation of the type of flow as well as storage of 3D volumes for blinded offline assessment is required. The lower segment–bladder boundary should be assessed with grayscale and color flow mapping. All features should be assessed blindly. Significant interobserver variability in the diagnosis of invasive placentation has been reported when examiners were blinded to clinical data43. The European group on invasive placentation is sharing their experiences of women with suspected MAP as a first step towards developing consensus for the diagnosis and management of this condition. Recently, standardized ultrasound descriptors44 and reporting45 for abnormally invasive placenta have been suggested based on consensus amongst experts, with a focus on unambiguous definition, in a move towards universally agreed terminology. However, there is still the problem of subjectivity in the description of several features, such as ‘increased’ vascularity and ‘irregularity’ of the bladder interface, which remain otherwise undefined. Assessment of the predictive accuracy of these signs will continue to be difficult without agreement as to what constitutes clinically relevant MAP. To this end, we propose a consistent clinical definition of abnormal placental invasion, imaging terminology and pathological criteria (Table 3). This terminology deliberately avoids the term ‘accreta’ because the aim is to identify disorders associated with major maternal morbidity/mortality. Whilst definitive antenatal diagnosis of MAP may not be possible, by developing scoring systems and assigning weight to individual signs depending on their positive likelihood ratios, improved detection and management should be possible. Such future developments should be on the basis of robust data rather than logic, reasoning or consensus of ‘experts’.