Clinical insights into placenta accreta spectrum: a comprehensive review

Abstract

Placenta accreta spectrum (PAS) is defined by abnormal placental adherence or invasion into the myometrium or adjacent organs and is a leading cause of massive obstetric hemorrhage. Its global incidence is increasing due to rising cesarean delivery rates, uterine surgeries, and the use of assisted reproductive technologies. This review summarizes the current knowledge regarding PAS, including its pathophysiology, risk factors, diagnostic methods, treatment options, and pregnancy outcomes after conservative management. The underlying pathogenesis is related to defective decidualization at the endometrial-myometrial interface, which is commonly associated with uterine scarring. Prenatal diagnosis relies on a thorough clinical history and imaging tools such as ultrasound and magnetic resonance imaging. Management strategies depend on fertility preservation goals and range from hysterectomy to conservative approaches such as leaving the placenta in situ. Effective management requires early risk identification, prenatal screening, referral to specialized centers, and delivery planning by a multidisciplinary team. Despite recent advances in imaging and surgical techniques, PAS remains the leading cause of maternal mortality and morbidity worldwide. There is a critical need for multicenter studies, standardized risk stratification tools, and long-term follow-up studies to optimize care and improve maternal and reproductive outcomes.

Introduction

Placenta accreta spectrum (PAS) refers to abnormal adherence or invasion of the placenta into the myometrium, preventing normal separation after childbirth. It is a major cause of severe postpartum hemorrhage (PPH) and maternal morbidity. Its global incidence has sharply increased in parallel with the rising rates of cesarean delivery, placenta previa, and other uterine surgeries [1,2]. Uterine scars, often resulting from cesarean delivery or myomectomy, are believed to create defects at the endometrial-myometrial interface. When placental implantation occurs in these areas, abnormal trophoblast infiltration and anchoring of villi adhesions may contribute to PAS development. PAS, previously termed morbidly adherent placenta or abnormally invasive placenta, encompasses a spectrum of conditions with varying degrees of villous invasion of the myometrium. Although the sensitivity and specificity of prenatal diagnosis have improved with the use of ultrasound and magnetic resonance imaging (MRI) in high-risk pregnancies, it remains impossible to identify all cases antenatally, and unexpected massive hemorrhages at delivery remain common. In response to these challenges, major professional societies such as the Society for Maternal-Fetal Medicine (SMFM; 2021), the Royal College of Obstetricians and Gynecologists (RCOG; 2019), and the International Federation of Gynecology and Obstetrics (FIGO; 2018) have issued evidence-based guidelines to optimize diagnosis and management. This review aims to synthesize the current knowledge by drawing upon these guidelines and recent literature to provide a comprehensive overview of PAS diagnosis and management.

Incidence

The incidence of PAS is steadily increasing, which is largely attributed to an increase in the associated risk factors. In the U.S., the incidence dramatically increased from approximately 1 in 2,510 deliveries in 1970 to 1 in 272 deliveries in 2016 [3,4]. A population-based study published in 2021 reported a PAS incidence rate of 0.48% between 2013 and 2015 [5]. This upward trend in incidence appears to be influenced by demographic shifts such as advanced maternal age and the increased use of assisted reproductive technology (ART). Furthermore, improvements in the sensitivity of diagnostic tools have played a significant role [6]. Notably, advancements in imaging techniques since 2010, including high-resolution ultrasonography and MRI, have enhanced the prenatal detection rate of PAS. Consequently, this has led to an increase in the reported incidence, as milder cases that might have gone undiagnosed previously are now being identified. Interestingly, some studies have observed regional or ethnic variations with relatively low incidence rates reported in certain Asian countries [7,8].

Although somewhat dated, the most reliable domestic data on PAS in Korea were obtained from a retrospective pathology-based study conducted between 1995 and 1999. This study reported a PAS incidence of approximately 0.267% among all deliveries. Of these, placenta accreta accounts for 35%, placenta increta for 60%, and placenta percreta for 5% [9]. Although recent nationwide data on the PAS incidence in Korea are lacking, a Japanese nationwide prospective birth cohort study published in 2019 reported an incidence rate of approximately 0.6% [7]. Given the high prevalence of advanced maternal age and persistently high cesarean delivery rates in Korea, the actual incidence of PAS in the Korean population may exceed that observed in Japan.

Pathogenesis

The pathophysiology of PAS is primarily attributed to defective decidua rather than to inherently invasive trophoblasts. In normal pregnancy, extravillous trophoblast infiltration is arrested at the decidual spongiosus; however, surgical disruption, such as a prior cesarean scar, compromises the endometrial-myometrial interface, eliminating the inhibitory signals that normally restrain trophoblast invasion [10,11]. Recent reviews have indicated that dysregulation of angiogenic signaling, integrin expression, and hypoxia-inducible pathways exacerbates abnormal trophoblast invasion in PAS [12]. Other proposed mechanisms contributing to PAS include altered inflammatory response at the implantation site and abnormal angiogenesis. Some studies have suggested that an exaggerated or chronic inflammatory state in the uterine scar may promote the invasive properties of trophoblasts. Additionally, dysregulation of the expression of various adhesion molecules, growth factors, and cytokines at the maternalfetal interface can facilitate abnormal placental attachment and invasion [13,14]. Emerging evidence also highlights the abnormal expression of integrins, excessive activity of matrix metalloproteinases, and hypoxia-related signaling pathways, all of which may enhance defective decidualization and excessive trophoblast infiltration. Abnormal remodeling of the spiral arteries and altered vascular architecture within the scar tissue may also contribute to the unique pathological features observed in PAS. Abnormal uterine healing after a cesarean delivery may contribute to the development of PAS. Previous studies have suggested that single- or double-layer continuous uterine sutures may shorten the operative time and reduce blood loss by facilitating rapid closure of the incision site. However, excessive pressure on the myometrium and the ischemic effects of continuous suturing may impair optimal wound healing, although supporting evidence remains limited. Inadequate scar healing can reduce the protective barrier against trophoblast invasion, predisposing patients to PAS. A case-control study reported that continuous inner-layer uterine sutures were associated with a significantly increased risk of PAS compared with interrupted sutures, possibly due to localized ischemia and scar formation. The adjusted odds ratio (OR) for PAS in patients with continuous sutures was 6.0 (95% confidence interval [CI], 1.4–25.2; P=0.015). These findings support the hypothesis that excessive tightening or non-physiological closure may impair endometrial regeneration and predispose patients to abnormal placental attachment [15]. These combined factors lead to the failure of physiological decidual separation during the third stage of labor, resulting in massive hemorrhage upon attempted manual removal of the placenta.

Risk factor

The most well-established pathophysiological mechanism of PAS is the failure of normal decidualization due to a defect in the endometrial-myometrial interface. This defect is often caused by uterine scarring from previous surgeries such as cesarean delivery, myomectomy, adenomyomectomy, or dilation and curettage. These procedures are recognized as risk factors of PAS.

1. Cesarean delivery

The global increase in cesarean delivery rates is strongly associated with the rising incidence of PAS, a fact well-documented in numerous studies [16,17]. A matched case-control study conducted in the U.S. in 2005 reported that the incidence of PAS after cesarean delivery increased from 12.5% in 1982 to 23.5% in 2002 [3]. Similarly, a cohort study from Hong Kong in 2015 observed an increase in PAS disorder from 0.17 per 1,000 deliveries in 1999–2003 to 0.79 per 1,000 deliveries in 2009–2013 [18]. A recent meta-analysis reported a summary OR of 1.96 (95% CI, 1.41–2.74) for PAS following a single cesarean delivery [19].

The risk of PAS increased significantly with the number of previous cesarean deliveries. A large prospective cohort study conducted in the U.S. in 2014 found that patients with two or three prior cesarean deliveries had an adjusted OR for accreta of 7.7 (95% CI, 2.4–24.9) [20]. Furthermore, a large population-based pregnancy cohort study published in 2016 reported ORs for PAS of 8.6 (95% CI, 3.5–21.1) for one prior cesarean, 17.4 (95% CI, 9.0–31.4) for two, and a substantial increase to 55.9 (95% CI, 25.0–110.3) for three or more prior cesarean deliveries [21]. Beyond the number of previous cesarean sections, a classical hysterotomy incision has also been reported to increase the risk of PAS compared to a low-segment hysterotomy incision [22].

When cesarean scar pregnancy (CSP) occurs as a result of prior cesarean delivery, the risk of subsequent PAS increases substantially. CSP is considered a significant precursor of PAS. CSP occurs when a gestational sac implants within the fibrous scar of a previous cesarean section, impairing normal decidualization. This abnormal implantation and defective decidual layer facilitate direct placental invasion of the myometrium [23]. Histologically, CSP and PAS share a similar spectrum of defective decidualization and abnormal trophoblastic invasion at scar sites. Accordingly, CSP has been classified into two main types: endogenic (type 1), in which the gestational sac grows toward the uterine cavity, and exogenic (type 2), in which the sac deeply invades the myometrium or bladder wall; the latter is strongly associated with progression to PAS [24]. More recently, an updated classification has been proposed, refining the diagnostic criteria and emphasizing its role as an early stage of PAS [25].

2. Myomectomy and adenomyomectomy

Although clear evidence directly linking myoma or adenomyosis to invasive placentation is limited, major uterine surgeries such as myomectomy and adenomyomectomy share a pathophysiological mechanism similar to that of cesarean delivery in predisposing patients to PAS. A nationwide cohort study investigating the incidence of PAS after myomectomy reported an incidence of 0.96% in women with a history of myomectomy compared to 0.20% in those without, yielding an adjusted OR of 2.28 (95% CI, 1.85–2.81) [26]. Although large-scale studies specifically on the incidence of PAS after adenomyomectomy are currently lacking, some smaller reports have indicated a trend towards increased PAS incidence following this procedure [27].

3. Placenta previa

Placenta previa is another critical risk factor for PAS. It is estimated to occur in approximately 1 in 200–300 births and notably, approximately 11% of women with placenta previa also have concomitant PAS [28]. A recent systematic review and meta-analysis found that PAS without previa is generally less severe, with a lower risk of invasive placenta (OR, 0.24), reduced blood loss (mean difference, 1.19 L), and fewer hysterectomies (OR, 0.11) [29]. The incidence of placenta previa increases with a history of previous cesarean deliveries and the risk further escalates with subsequent cesarean delivery [30]. Consequently, the combination of a history of cesarean delivery and placenta previa dramatically increases the incidence of PAS. While PAS occurs in approximately 4% of cases with placenta previa but no prior cesarean deliveries, its incidence surges to between 50% and 67% when placenta previa is combined with three or more previous cesarean deliveries [31].

4. Other risk factors

Several other conditions and procedures have also been reported as risk factors for placenta accreta, including uterine anomalies, endometritis, ART, uterine artery embolization (UAE), chemotherapy, and radiation [20,32–34]. Uterine curettage, endometrial ablation, and hysteroscopic surgery can cause myometrial defects and scarring, thereby increasing the risk of developing PAS in future pregnancies [35,36]. ART is also a potential contributor to PAS. The mechanisms may involve poor decidualization due to suboptimal preparation, a thin endometrium, or repeated injury [37,38]. Additionally, abnormal implantation in the lower uterine segment or cesarean scar sites during embryo transfer may predispose to PAS [39]. ART pregnancies often involve multiple uterine anomalies, which may increase the risk of PAS. A 2012 UK Obstetric Surveillance System study reported an adjusted OR of approximately 32.1 (95% CI, 2.0–509) for PAS disorders in in-vitro fertilization pregnancies [40]. However, a recent meta-analysis of cohort studies reported no significant difference in the relative risk between ART and spontaneous singleton pregnancies [41], suggesting that further research is warranted to clarify this association. According to a retrospective cross-sectional study of 2,223 women with histologically verified PAS disorders, prior endometritis was independently associated with a three-fold increased risk of PPH (OR, 3.01; 95% CI, 1.06–9.02). This suggests that infection-related damage may worsen placentation and bleeding risk in patients with PAS. Although this study primarily investigated PPH, the observed link supports the role of endometrial inflammation in the pathophysiology of PAS [42].

Classification

While the definitive diagnosis of PAS is ultimately established by histopathology, clinical practice often involves prenatal or intraoperative diagnoses due to efforts to preserve the uterus through various surgical techniques and conservative management, such as UAE, before resorting to cesarean hysterectomy. Consequently, the number of cases diagnosed prenatally or intraoperatively significantly outweighed the number of cases confirmed histopathologically.

The FIGO recently introduced a comprehensive grading system for diagnosing PAS (Table 1).

Table 1.

General classification of PAS from the FIGO grading system [79]

Grade 1: abnormally adherent placenta (placenta adherent or creta)

Clinical criteria

At vaginal delivery

No separation with synthetic oxytocin and gentle controlled cord traction

Attempts at manual removal of the placenta results in heavy bleeding from the placental implantation site requiring mechanical or surgical procedure

If laparotomy is required (including for cesarean delivery)

Same as above

Macroscopically, the uterus show no obvious distension over the placental bed (placental “bulge”), no placental tissue is seen invading through the surface of the uterus, and there is no or minimal neovascularity

Histologic criteria

Microscopic examination of the placental bed samples from hysterectomy specimen shows extended areas of absent decidua between villous tissue and myometrium with placental villi attached directly to the superficial myometrium

The diagnosis cannot be made on just delivered placental tissue nor on random biopsies of the placental bed

Grade 2: abnormally invasive placenta (increta)

Clinical criteria

At laparotomy

Abnormal macroscopic findings over the placental bed: bluish/purple coloring, distension (placental “bulge”)

Significant amounts of hypervascularity (dense tangled bed of vessels or multiple vessels running parallel craniocaudially in the uterine serosa)

No placental tissue seen to be invading through the uterine serosa

Gentle cord traction results in the uterus being pulled inwards without separation of the placenta (so-called the dimple sign)

Histologic criteria

Hysterectomy specimen or partial myometrial resection of the increta area shows placental villi within the muscular fibers and sometimes in the lumen of the deep uterine vasculature (radial or arcuate arteries)

Grade 3: abnormally invasive placenta (percreta)

Grade 3a: limited to the uterine serosa

Clinical criteria

At laparotomy

Abnormal macroscopic findings on uterine serosal surface (as above) and placental tissue seen to be invading through the surface of the uterus

No invasion into any other organ, including the posterior wall of the bladder (a clear surgical plane can be identified between the bladder and uterus)

Histologic criteria

Hysterectomy specimen showing villous tissue within or breaching the uterine serosa

Grade 3b: with urinary bladder invasion

Clinical criteria

At laparotomy

Placenta villi are seen to be invading into the bladder but no other organs

Clear surgical plane cannot be identified between the bladder and uterus

Histologic criteria

Hysterectomy specimen showing villous tissue breaching the uterine serosa and the bladder wall tissue or urothelium

Grade 3c: with invasion of other pelvic tissue/organs

Clinical criteria

At laparotomy

Placenta villi are seen to be invading into the broad ligament, vaginal wall, pelvic sidewall or any other pelvic organ (with or without invasion of the bladder)

Clear surgical plane cannot be identified between the bladder and uterus

Histologic criteria

Hysterectomy specimen showing villous tissue breaching the uterine serosa and invading pelvic tissues/organs (with or without invasion of the bladder)

PAS, placenta accreta spectrum; FIGO, International Federation of Gynecology and Obstetrics.

This system classifies PAS into three distinct grades (grade 1 to grade 3), each defined according to specific clinical and histological criteria. Grade 1 represents cases in which the placenta adheres to the myometrium and the adherence is abnormal. Grade 2 signified invasion of the myometrium. Grade 3, specifically designated as percreta, indicates full-thickness invasion through the myometrium, potentially involving the adjacent organs. Grade 3 is further subclassified into 3a, 3b, and 3c based on the extent and type of involvement of the surrounding structures, such as the serosa, bladder, or other pelvic organs. This standardized grading system aims to improve the consistency of diagnoses and guide management strategies.

Prenatal screening and diagnosis

The only way to definitively diagnose PAS is through histopathology, which can occur after the surgical removal of the uterus. In cases where there is an attempt to save the uterus but only part of the placenta shows abnormal adherence, a definitive histopathological diagnosis is often not possible and will instead remain clinically suspicious. Given the high risk of massive hemorrhage and maternal morbidity associated with PAS, antenatal identification and delivery planning in a specialized facility are necessary. This also emphasizes the importance of early prenatal diagnosis and the ability to stratify risks, especially during the first trimester. First-trimester ultrasonography is especially valuable in difficult cases early in pregnancy, such as the posterior placenta or percreta, as later imaging may underestimate the depth of invasion because of acoustic shadowing or limited visualization. Early detection under these circumstances increases the potential for accurate diagnosis and multidisciplinary preparation. Throughout pregnancy, ultrasound and MRI remain the primary imaging modalities used. While maternal serum markers like β-human chorionic gonadotropin (β-hCG), pregnancy-associated plasma protein A (PAPP-A), and alphafetoprotein (AFP) have been associated with PAS in some studies, their effectiveness as diagnostic tests is limited, and they are not recommended as standalone tools for screening. New biomarkers are being studied and require further clinical testing before being considered for practical use.

1. Obstetric sonography

Obstetric ultrasound is the primary and most essential tool for the prenatal diagnosis of PAS. However, diagnostic accuracy can be influenced by the examiner’s skill, gestational age, and equipment performance. While simple grayscale imaging alone has reported sensitivities ranging from approximately 50% to 87%, the addition of color Doppler imaging significantly improves the diagnostic accuracy. A recent systematic review and meta-analysis demonstrated that, when performed by highly experienced operators, ultrasound achieved a sensitivity of 90.72%, a specificity of 96.94%, and a diagnostic OR of 98.59 for PAS diagnosis [43]. Three-dimensional ultrasonography can also be used as an adjunct tool. The antenatal diagnosis of PAS was significantly higher in women with coexisting placenta previa (72.3%) than in those without (6.9%), highlighting the challenge of diagnosing PAS in the absence of previa (P<0.001) [44]. Therefore, PAS diagnosis cannot rely solely on ultrasound, as it has inherent limitations, particularly in the absence of placenta previa. The use of additional diagnostic tools is necessary to improve the detection accuracy. Sonographic features associated with placenta accreta have recently been systematically categorized by the International Society for PAS (Table 2).

Table 2.

IS-PAS unified descriptors for PAS disorders

US finding	IS-PAS suggested standardized definition
2D grayscale
Loss of ‘clear zone’	Loss, or irregularity, of hypoechoic plane in myometrium underneath placental bed (‘clear zone’)
Abnormal placenta lacunae	Presence of numerous lacunae including some that are large and irregular (finberg grade 3), often containing turbulent flow visible on grayscale imaging
Bladder wall interruption	Loss or interruption of bright bladder wall (hyperechoic band or ‘line’ between uterine serosa and bladder lumen)
Myometrial thinning	Thinning of myometrium overlying placenta to <1 mm or undetectable
Placental bulge	Deviation of uterine serosa away from expected plane, caused by abnormal bulge of placental tissue into neighboring organ, typically bladder; uterine serosa appears intact but outline shape is distorted
Focal exophytic mass	Placenta tissue seen breaking through uterine serosa and extending beyond it; most often seen inside filled urinary bladder
2D color Doppler
Uterovesical hypervascularity	Striking amount of color Doppler signal seen between myometrium and posterior wall of bladder; this sign probably indicates numerous, closely packed, tortuous vessels in that region (demonstrating multidirectional flow and aliasing artifact)
Subplacental hypervascularity	Striking amount of color doppler signal seen in placental bed; this sign probably indicates numerous, closely packed, tortuous vessels in that region (demonstrating multidirectional flow and aliasing artifact)
Bridging vessels	Vessels appearing to extend from placenta, across myometrium and beyond serosa into bladder or other organs; often running perpendicular to myometrium
Placenta lacunae feeder vessels	Vessels with high-velocity blood flow leading from myometrium into placental lacunae, causing turbulence upon entry
3D ultrasound±power Doppler
Intraplacental hypervascularity	Complex, irregular arrangement of numerous placental vessels, exhibiting tortuous courses and varying calibers

Modified from Collins et al. [80].

IS-PAS, International Society for placenta accreta spectrum; PAS, placenta accreta spectrum; US, ultrosound; 2D, two-dimensional; 3D, three-dimensional.

The “loss of clear zone” finding, while relatively easy to detect, has a notable drawback of a somewhat high false-positive rate of approximately 21% [45]. In contrast, abnormal placental lacunae, also known as the “Swiss cheese appearance” due to the vascular spaces within the placental parenchyma, boast a high sensitivity of 80–90% and a low false-positive rate. This makes it one of the most critical ultra-sound findings in the diagnosis of PAS. Identifying the turbulent blood flow within these lacunae using color Doppler also aids in predicting PAS. Furthermore, observing bladder wall interruption along with increased vascularity at the uterovesical interface using color Doppler provides highly sensitive and specific indicators of PAS [46]. Myometrial thinning, with approximately 93% sensitivity and 79% specificity, is another key sign of PAS and is often observed in conjunction with lacunae. For an accurate assessment of bladder wall interruption, placental bulging, and uterovesical hypervascularity, it is crucial to examine the bladder filled to 200–300 mL. Combining these various ultrasound findings allows the prediction of the PAS grade and extent of accreta placentation. According to a recent meta-analysis, ultrasound demonstrated a pooled sensitivity of approximately 90% and specificity of 97% for PAS diagnosis, with the highest accuracy when performed by experienced operators [47]. The current FIGO and American College of Obstetricians and Gynecologists (ACOG) guidelines recommend ultrasound as the first-line diagnostic modality, reserving MRI scans for equivocal or complex cases.

Although ultrasonography remains the cornerstone of PAS diagnosis, several antenatal scoring systems have been developed that integrate sonographic features (such as placental lacunae, myometrial thinning, and loss of the clear zone) with clinical risk factors to improve predictive accuracy. These models, such as the placenta accreta index (PAI), can support early recognition of high-risk patients, although their broader clinical utility lies in referral and management planning.

2. MRI

MRI is highly valuable for diagnosing PAS, offering sensitivity and specificity comparable to those of ultrasonography. It is particularly effective when the placenta is located posteriorly, which makes ultrasound assessment challenging. Furthermore, MRI provides superior evaluation of myometrial involvement, bladder invasion, and depth of placental invasion compared to ultrasound. The optimal timing for MRI is generally between 24 weeks and 30 weeks of gestation [48]. Intravenous contrast agents are typically not administered during prenatal MRI due to concerns regarding fetal toxicity. MRI findings of PAS include both direct signs, which indicate abnormal placental invasion, and indirect signs, which indicate secondary effects on the placental parenchyma or vasculature [49].

Compared with ultrasound, MRI demonstrates a pooled sensitivity of 83% and a specificity of 84%; however, interobserver variability remains higher, and diagnostic accuracy is more dependent on expertise [47,50]. MRI is most useful when ultrasound findings are inconclusive, particularly for posterior placentation, maternal obesity, or when parametrial or bladder invasion is suspected. Thus, the guidelines emphasize MRI as a complementary problem-solving tool, rather than as a routine screening modality.

On MRI, indirect indicators of PAS include placental heterogeneity, T2 dark bands, and abnormal hypervascularity characterized by tortuous, ectatic intraparenchymal vessels and proliferated retroplacental or pelvic veins. Direct signs comprise focal defects in the myometrial wall and bladder tenting, while unequivocal invasion into adjacent organs is highly suggestive of placenta percreta [49].

Placental bulging is identified as a deviation of the uterine serosa away from its expected plane. This sign is considered the most useful when observed in isolation. It can appear either focally or diffusely, with diffuse bulging potentially altering the normal inverted-pear shape of the uterus [51]. Placental heterogeneity is a subjective concept and its degree is determined by an interpreting radiologist. As an indirect sign of PAS, it involves an overall assessment of the placental condition. It manifests as a mixture of abnormal intraplacental hypervascularity, irregular or undulating contours, and T2 dark bands. T2 dark bands appear as bands traversing the perpendicular axis of the placenta, often originating from the maternal surface and extending towards the fetal surface with variable thickness. These bands were thought to represent fibrin deposition. Intraplacental hypervascularity requires careful differentiation from normal placental vascularity. Abnormally hypervascular areas typically exhibit enlarged intraparenchymal vessels that appear bizarre, disorganized, or ectatic. The absence of the typical uterine trilaminar layer (hypo-hyper-hypointense signal) due to focal interruptions in the myometrial wall suggests PAS. However, identifying myometrial line disruption along the entire uterine wall can be challenging, leading to an increased risk of false positives. Bladder stenting, defined as the elongation of the bladder dome towards the uterine wall, is another important sign. The thinning and irregularity of the normally hypointense bladder wall suggested bladder invasion. The presence of extrauterine invasion, such as invasion into the bladder or adjacent structures or a focal exophytic mass, strongly suggests placenta percreta.

3. Prenatal biomarker for PAS

At 11–12 weeks of gestation, lower levels of β-hCG and higher levels of PAPP-A have been associated with an increased risk of PAS. In the second trimester, maternal serum AFP and β-hCG levels exceeding 2.5 multiples of the median compared to normal pregnancies have also shown a significant association with PAS [34,52]. In contrast, cell-free fetal DNA testing did not demonstrate significant differences between pregnancies affected by PAS and those with normal placentation [53]. Due to the limited diagnostic accuracy of these serum markers, they are not recommended as standalone clinical screening tools for PAS.

4. Emerging trends in PAS diagnosis

Recent advances are beginning to reshape the diagnostic paradigm for PAS. Machine learning and radiomics models that automatically analyze imaging features have shown promise. In a recent pilot study, machine learning algorithms applied to ultrasound images achieved promising discrimination between patients with PAS and healthy controls [54]. Another model combining MRI radiomics and clinical signatures reported an accuracy of up to 0.825, a sensitivity of 0.830, and a specificity of 0.822 in an external validation cohort for PAS detection [55]. Simultaneously, molecular biomarkers are currently being investigated. A systematic review of new molecular biomarkers (transcriptomics, genomics, and protein-based markers) highlighted several candidate markers (e.g., miRNAs and growth factors) that may distinguish abnormal placentation from normal pregnancies, although most remain experimental [56]. Although these approaches are not yet a part of standard care, predictive models that integrate imaging, clinical data, and molecular markers have the potential to improve risk stratification and individualized diagnosis. Continued research and prospective validation are essential before widespread clinical adoption.

Management

The management of PAS is broadly categorized as antepartum, intrapartum, and postpartum. Furthermore, it can be classified as either conservative (aimed at fertility preservation) or nonconservative (surgical) management, depending on the goal of preserving future fertility. The ideal therapeutic strategy for patients with PAS involves planned delivery at a tertiary care hospital, with the active involvement of a multidisciplinary care team comprising specialists from obstetrics, anesthesiology, urology, and critical care. When properly implemented, this comprehensive approach can significantly improve maternal outcomes, even in severe cases of PAS.

1. Antepartum management

1) Patient selection

Although PAS can sometimes be an unexpected intrapartum diagnosis, the most critical step before delivery is to identify individuals at risk for PAS. History taking to uncover relevant risk factors plays a crucial role in the screening of these patients. Confirming the history and number of previous cesarean deliveries, other major or minor uterine surgeries, or current pregnancy status via ART facilitates the identification of sonographic signs suggestive of PAS. Once appropriate candidates are identified based on their history, further screening involves the identification of PAS-specific signs via ultrasound or MRI to select those with a strong suspicion of PAS. At this stage, maternal biomarkers such as AFP and β-hCG can also be checked.

2) Risk stratification and scoring systems

Accurate antenatal risk stratification is an important component of PAS management. In addition to recognizing traditional risk factors, structured scoring systems have been proposed to improve predictions and guide referrals. One such model is the PAI, which integrates clinical history (e.g., number of prior cesarean deliveries and placental location) with ultrasound findings such as placental lacunae, loss of the clear zone, and myometrial thickness. Validation studies have demonstrated that higher PAI scores are associated with an increased probability of PAS and greater disease severity [57]. Recently, other ultrasound-based scoring systems have been proposed. For example, Zhang et al. [58] developed a multiparameter scoring system incorporating placental lacunae, myometrial thinning, bladder wall interruption, and bridging vessels, reporting an area under the curve of 0.93 for PAS prediction. Similarly, Pekar Zlotin et al. [59] evaluated a clinical-sonographic score combining patient risk factors with imaging features and demonstrated improved accuracy in stratifying patients at high risk of PAS. Although none of these tools have been universally adopted, they are increasingly being utilized in tertiary centers to aid early referral to specialized PAS care units and to support multidisciplinary delivery planning. Future studies are required to validate their performance across diverse populations and standardize their application in clinical practice.

3) Transfer to a center of excellence

Once a high-risk patient is identified, delivery transfer should be considered. The transfer should be to a facility equipped with a multidisciplinary team. Optimal management of PAS relies on a coordinated multidisciplinary team. Anesthesiologists ensure perioperative hemodynamic stability and require massive transfusion. Urology assists with bladder or ureteral involvement, including stenting or surgical repair. Interventional radiology may provide adjunctive control of the hemorrhage through balloon occlusion or embolization in selected cases. Blood bank coordination is essential for the timely preparation and rapid availability of blood products. Early referral to specialized centers, where such expertise is available, is crucial for improving maternal outcomes. Additionally, the center should have 24-hour access to a surgical or medical intensive care unit and a neonatal intensive care unit, along with the capacity for rapid blood transfusion to manage massive hemorrhage [60].

4) Time of delivery

For women with suspected PAS, the delivery method is planned cesarean delivery. The optimal timing for such planned deliveries must carefully balance maternal risks with neonatal benefits. One study reported that approximately 40% of women diagnosed with PAS experienced unplanned deliveries due to bleeding before 34 weeks of gestation [61]. Therefore, the ACOG recommends delivery between 34 weeks and 0 days and 35 weeks and 6 days [32]. Similarly, the SMFM recommends that in asymptomatic patients with confirmed PAS, a planned cesarean hysterectomy should be scheduled between 34+0 weeks and 35+6 weeks of gestation [62]. If vaginal bleeding commences earlier, antenatal corticosteroid administration should be considered depending on the clinical situation. The RCOG suggests planned delivery at 36+0-37+0 weeks in stable patients, while early delivery between 34+0 and 36+6 weeks should be considered in cases with an increased risk of bleeding or spontaneous labor [63]. The FIGO acknowledges delivery between 34+0 weeks and 36+6 weeks as reasonable for most PAS cases and recommends earlier intervention in the presence of maternal or fetal complications [47].

2. Intrapartum and postpartum management

Table 3 outlines the recommended management strategies for PAS according to the FIGO staging.

Table 3.

Suggested management strategies according to FIGO grading of PAS

FIGO grade	Suggested management
Grade 1 (accreta/creta)	Conservative or uterus-preserving approaches may be considered in selected cases (e.g., local resection, repair)
Grade 2 (increta)	Cesarean hysterectomy is the preferred treatment when invasion is deeper; conservative management may only be attempted in highly selected settings
Grade 3a (percreta limited to serosa)	In most cases, the placenta should not be removed and cesarean hysterectomy should be planned
Grade 3b (percreta with bladder invasion)	Hysterectomy with partial cystectomy or urologic reconstruction should be anticipated when invasion of the bladder is present (implied in FIGO invasive percreta management)
Grade 3c (percreta with extension to other pelvic organs)*	Multidisciplinary surgery with possible exenterative approach is required in extensive organ invasion (supported by FIGO statements on advanced percreta)

FIGO, International Federation of Gynecology and Obstetrics; PAS, placenta accreta spectrum.

1) Nonconservative surgical management

Cesarean hysterectomy is often the primary treatment for prenatally diagnosed PAS. In regions where additional conservative management is not readily available, cesarean hysterectomy is the most appropriate treatment option. This method involves delivering the fetus while leaving the placenta in situ within the uterus, which helps reduce immediate massive hemorrhage from attempted placental removal. Approximately 80–90% of PAS diagnoses lead to either emergent or elective cesarean hysterectomy [64]. Hysterectomy is particularly common when placenta increta or percreta is suspected.

Significant blood loss, typically ranging from 2–3 L, is anticipated during a cesarean hysterectomy. Therefore, meticulous preoperative preparation, including the availability of a cell saver and close collaboration with a blood bank for timely transfusion, is essential. Antifibrinolytic agents such as tranexamic acid can be administered prophylactically or during hemorrhage. A recent large, multicenter, international randomized clinical trial reported that tranexamic acid could reduce maternal mortality in PPH [65]. While some reports have suggested a reduction in bleeding when prophylactically administered during cesarean deliveries, further research is needed in this area.

A multidisciplinary team must also be readily available to manage potential complications such as bladder or ureteral injury, other organ damage, massive hemorrhage, and infection. The utility of prophylactic ureteral stent placement in PAS remains controversial, particularly in cases of suspected bladder or ureteric invasion. The ACOG and the SMFM do not recommend routine use but advise that ureteral stenting be considered on a case-by-case basis when genitourinary tract involvement is suspected, especially in percreta cases [32]. A recent systematic review and meta-analysis concluded that prophylactic ureteral stenting did not significantly reduce the incidence of urinary patients with PAS, suggesting a limited benefit from routine use [66]. These conflicting findings highlight the need for further prospective studies to clarify the role of ureteral stenting in patients with PAS. Taken together, although universal prophylactic use is not currently endorsed, selected applications in high-risk PAS cases may be a useful adjunct to minimize urological complications. Intra-arterial balloon occlusion (IABO) has been increasingly used as an adjunctive strategy in the surgical management of placenta accreta. By temporarily reducing pelvic arterial blood flow, IABO can decrease intraoperative blood loss and improve visualization of the surgical field during cesarean hysterectomy. A large observational study from Scandinavia reported that IABO during cesarean hysterectomy was associated with reduced estimated blood loss and lower transfusion requirements, although the overall impact on maternal morbidity remains debated [67]. Despite the potential benefits, risks such as vascular injury, thrombosis, and limb ischemia must be considered, and its use is generally recommended in specialized centers with interventional radiology expertise. Anesthesia for surgery was chosen based on the patient’s condition and circumstances, including general or regional/neuraxial anesthesia. Although general anesthesia is generally preferred, regional anesthesia (epidural or spinal) is increasingly used. Several studies have indicated that conversion from regional to general anesthesia due to increased blood loss or prolonged surgical time occurs in approximately 8–45% of cases [68,69]. While neonatal outcomes are reported to be better with regional anesthesia than with general anesthesia, maternal outcomes, such as blood loss and transfusion rates, vary across different literature [68–70].

For skin incisions, a midline abdominal incision is generally preferred to ensure a wide surgical field, although some operators, such as Maylard, may opt for transverse incisions. The hysterectomy approach can vary depending on the placental location, and it is generally safer to make incisions to avoid the placentation site. There was an approximately 50/50 split in the preference between total and subtotal hysterectomies. Total hysterectomy offers the long-term benefit of preventing cervical malignancy, whereas subtotal hysterectomy may offer advantages in terms of reduced intraoperative blood loss and recovery. However, in cases of cervical involvement, such as those with placenta previa, total hysterectomy is a more advisable approach.

2) Conservative management

Conservative management of PAS is primarily undertaken to preserve fertility and maintain the patient’s self-esteem by avoiding hysterectomy. This approach can be broadly divided into two main strategies: attempting placental removal and leaving the placenta in situ within the uterus. Other adjunctive methods, such as UAE, methotrexate therapy, hemostatic sutures, pelvic devascularization, and balloon tamponade, have also been explored.

① Uterine preservation and placental removal

Placental removal typically involves manual removal, which is commonly encountered when PAS is not diagnosed prenatally. This approach carries a significant risk of massive hemorrhage, potentially leading to life-threatening scenarios. If bleeding becomes uncontrollable, a subsequent unavoidable hysterectomy may be necessary after placental removal. Furthermore, even if initial bleeding is controlled, rebleeding can occur postpartum, necessitating preparedness for additional management strategies such as UAE.

② Excision of the placenta using an in situ approach

This method involves leaving the placenta within the uterus and awaiting spontaneous resorption. A retrospective multicenter study reported that of 167 cases managed with conservative therapy, 131 women (78.4%; 95% CI, 71.4–84.4%) had successful outcomes, while the remaining 36 underwent either primary hysterectomy (18 cases) or delayed hysterectomy (18 cases). Spontaneous placental resorption occurred among 87 out of 116 women (75%; 95% CI, 66.1–82.6%), with a median delay from delivery of approximately 13.5 weeks (range 4–60 weeks) [71]. Other studies have reported that approximately 20% of women require hysterectomy after conservative management [72,73].

A retained placenta rarely leads to complications such as coagulopathy or septicemia, necessitating careful monitoring. Weekly monitoring of serum β-hCG levels is recommended for the first 2 months, followed by monthly checks to confirm placental resorption. However, additional MRI is generally not recommended. Several methods have been proposed to aid the resolution of retained placental fragments. One method involves the administration of methotrexate (MTX). A recent observational case series involving 24 women with retained placenta in situ who received MTX reported placental expulsion in approximately 33.3% of cases, with 55% spontaneous and 45% achieved by dilation and curettage [74]. However, research is still limited, and considering the potential adverse effects of MTX, such as neutropenia and medullary aplasia, its routine use has not yet been recommended. Hysteroscopic resection has also been proposed for removing retained placental fragments. Although it is generally successful, its benefit in asymptomatic women remains unclear.

Surgical or radiological uterine devascularization techniques are employed to reduce PPH in patients with PAS. These methods include bilateral uterine or hypogastric artery ligation, iliac artery embolization, or balloon occlusion. Prophylactic embolization reduces intraoperative blood loss and subsequent hemorrhage [75,76]. However, the efficacy of prophylactic balloon catheter placement in the iliac arteries or aorta in patients with PAS remains controversial.

Obstetrics and fertility outcome

Women with successfully preserved uteri may consider future pregnancies. However, in those with a history of PAS disorders, the risk of recurrence in subsequent pregnancies has been reported to be approximately 22–29% [77,78]. Additionally, intrauterine adhesions and secondary amenorrhea, both of which may impair fertility, were observed in approximately 8.3% of these cases [78].

Conclusion

PAS remains a leading cause of obstetric hemorrhage and maternal morbidity. Its incidence continues to increase, largely in parallel with increasing cesarean delivery rates, uterine surgeries, and assisted reproductive technologies. Antenatal recognition through careful risk assessment and imaging, followed by referral to centralized high-risk care centers and multidisciplinary management, is critical for improving outcomes. Although conservative options may preserve fertility in selected cases, recurrence rates and long-term complications remain significant. Future randomized controlled trials and longitudinal studies on fertility outcomes are urgently required to establish optimal management strategies.