Key points are not available for this paper at this time.
Recent advances in imaging techniques, medical genetics and clinical biology have enabled clinicians to screen for various adverse outcomes, such as aneuploidy1-4, pre-eclampsia5-7 and preterm birth8-10, with potentially huge impact on short- and long-term maternal and fetal wellbeing. Indeed, the introduction of such screening techniques in obstetrics has led to significant reductions in the incidence of certain conditions. For example, first-trimester measurement of nuchal translucency is a well-established screening modality for Down syndrome and other aneuploidies, detecting 64–70% of cases11, and enabling evidence-based counseling and clinical management. The sensitivity of detection improved with the introduction of sequential screening using first-trimester ultrasound and first- as well as second-trimester serum markers (90% detection), and subsequently improved even further with the advent of cell-free DNA testing, which allowed screening as early as 10 weeks' gestation, with 99% sensitivity12. These advances in screening have improved our ability to offer prenatal, or immediate neonatal, targeted therapy1-4. To take another example, routine screening for pre-eclampsia, with thorough maternal history-taking, biochemical-marker measurement and uterine artery Doppler assessment, has improved the prediction of this hypertensive disorder, thus facilitating the use of aspirin prophylaxis in high-risk patients, a course of action which, when initiated prior to 16 weeks of gestation, has proved efficacious in the prevention of pre-eclampsia5-7, 13. The increased rate of Cesarean deliveries throughout the last decade is well documented14. Concomitantly, obstetricians and gynecologists across the world have encountered an increasing number of complications in women conceiving and carrying pregnancies after one or more previous Cesarean sections. These complications involve a range of pathologies, of which pathologically adherent placenta, lately termed placenta accreta spectrum (PAS) by a consensus panel of the International Federation of Gynecology and Obstetrics (FIGO), is the most relevant clinically15. It is also well documented that Cesarean delivery is associated with a significant impact on future pregnancy, including an increased risk of both short- and long-term complications, such as profuse overt and intra-abdominal hemorrhage, PAS, uterine rupture and gravid hysterectomy16-20. PAS is also known by several alternative terms (such as morbidly adherent placenta, abnormally invasive placenta and placental adherence disorder), used by different organizations in various countries, as well as by different journals; for the purposes of this Opinion article, we will use the term suggested by FIGO, i.e. PAS15. This pathological entity may have devastating consequences, and presents affected women and their healthcare providers with unique diagnostic and therapeutic challenges. Yet, there is no established guideline for how and when to screen these women. A proposal for early screening for Cesarean section-related morbidity has been documented previously by El-Refaey et al.21. In the present article, we show why such early screening would be beneficial. This Opinion was conceived by clinicians who, in addition to having academic and research interests in the subject, have had the opportunity to care for a significant number of patients with such unusual pregnancies. Drawing on our experience of affected pregnancies at a variety of gestational ages, it has become obvious that early, accurate clinical and sonographic evaluation of a pregnancy after a previous Cesarean delivery can facilitate not only timely counseling, but also, if needed, gestational age-appropriate individualized pregnancy management. Supported by statements and conclusions found in a wide range of publications, we advocate early (specifically, between 5 and 7 weeks' gestation) evaluation of pregnant women with prior Cesarean section, via early confirmatory urine or serum human chorionic gonadotropin (hCG) testing and an early transvaginal ultrasound (TVS) examination. Our focus in this Opinion is the faulty implantation of a fertilized oocyte into a niche or on a uterine scar created by hysterotomy at the time of a previous Cesarean delivery. This type of unusual gestation is, aptly, termed a Cesarean scar pregnancy (CSP); in the literature, terms such as ‘Cesarean ectopic pregnancy’ and ‘isthmic pregnancy’ are also used. Our agreed view is that the correct term should be CSP, since the implantation is in the lowest area of the cavity and, in contrast to true ectopic pregnancies, a CSP may yield a live neonate. The term ‘ectopic’ should be avoided in these cases, since such descriptors may lead to treatments that are inappropriate for this type of pathology. Many clinicians consider CSP to be a rare occurrence, with its reported rate being from 1 in 800 to 1 in 2500 pregnancies20. However, this reported incidence of CSP is at best an estimation and is influenced by many confounding factors, such as population heterogeneity, Cesarean delivery rates and time to diagnosis14, 16. Regardless of the accuracy of the aforementioned incidence, it is important to anticipate that the rising rate of Cesarean deliveries will likely be accompanied by an increase in the incidence of CSP. Whilst evaluation of a scar from a previous Cesarean section has been reported previously, its clinical value has largely been unrecognized16-18, 22. Yet, failure to identify a CSP (with or without PAS) can have catastrophic consequences. In a systematic review, we included 46 cases from 45 individual articles reporting severe complications from CSP; most of these cases were undiagnosed or misdiagnosed, ultimately leading not only to loss of the pregnancy, but also, frequently, to hysterectomy with loss of fertility, due to PAS and uncontrollable hemorrhage16. One study reported a rate of up to 36% for misdiagnosis of CSP as an early miscarriage in the setting of painful vaginal bleeding, elevated hCG and presence of a cystic mass in the lower uterine segment23. A search of the literature for cases with significant complications resulting from management of both undiagnosed and diagnosed CSPs revealed an increasing number of communications in recent years. The most relevant articles, published between 1978 and the present, are summarized in Table 124-40. In light of such a high rate of misdiagnosis or treatment failure and the lack of a standardized approach to early screening for these abnormal pregnancies, it is all the more concerning that, if an undiagnosed or misdiagnosed CSP is allowed to continue, it can result in loss of the uterus and sometimes even in maternal death25, 33. The early detection of a CSP facilitates early assessment for invasive placentation, which is potentially lethal34. Fortunately, two easily applicable methods are available to facilitate the diagnosis of CSP and differentiate it from a correctly implanted intrauterine pregnancy41-43. These use evaluation of sagittal ultrasound images to determine the location of the center of the gestational sac relative to transverse43 and/or longitudinal41,42 lines that are placed specifically on the image to mark the lower and/or anterior halves of the uterus21, 22. These methods work best if applied in the early first trimester, since after that point, the growing gestational sac begins to fill the uterine cavity, distorting the location of initial implantation, although the placenta and associated vessels remain in place; such assessment has up to 98.9% specificity and 93% sensitivity when used between 5 and 10 weeks' gestation41-43. Using these simple sonographic methods, early diagnosis and evaluation of CSP may provide clues to the natural progression of, and/or best management approaches to, these unusual gestations. For example, it has been demonstrated that for CSP cases without detectable fetal cardiac activity, the majority (approximately 69%) result in spontaneous uncomplicated miscarriage; only about 31% of these cases required intervention44. In contrast, a CSP with a fetal heart beat detected in the first trimester has a very different prognosis. These pregnancies are at high risk for severe bleeding and clinical symptoms requiring first-trimester surgical and/or medical intervention: in a review of the literature, uncomplicated miscarriage occurred in only about 13% of such women, while 20% required surgical management, and in the first and second trimesters of pregnancy, rupture of the uterus occurred in 9.9% of cases and hysterectomy was necessary in 25.2%. Furthermore, about a third of such CSPs progressing to the third trimester were complicated by hemorrhage and, at the time of delivery, 75% had pathologic diagnosis of PAS, mostly placenta percreta44. The use of sonography early in pregnancy to diagnose CSP is not a new concept. Comstock et al.45 stated as early as 2003 that their ‘results suggest that sonographic findings can also be used to identify patients at risk for placenta accreta as early as the first trimester of pregnancy’. In the same year, Jurkovic et al.46 wrote: ‘…transvaginal ultrasound has been used in most studies and is likely to emerge as a future gold standard for the diagnosis of scar implantation. Diagnosis is relatively simple early in pregnancy…’. Furthermore, Zosmer et al.47 reported on 10 pregnancies implanted in or on a Cesarean scar, diagnosed in the first trimester and followed to near term. The median age at diagnosis of CSP was 7 weeks and 5 days, though the diagnosis was already suspected at 5 or 6 weeks in at least four cases. They commented on sonographic indicators for prognosis and the natural history of these gestations as follows: ‘Complete implantation within the myometrial defect, bulging of the trophoblast out of the uterine contour and large placental lakes in the first trimester are ultrasound findings that may predict a severe placenta accreta or percreta and consequently a poor outcome.’. Rarely is first-trimester diagnosis of PAS reported, since there is no consensus on which early marker (or combination of markers) for PAS should be considered truly predictive early in pregnancy48, 49. However, several studies have illustrated that low anterior sac position within the niche (or on the hysterotomy scar), thin (or no) myometrial thickness, early appearance of placental lacunae and hypervascularity at the uterus–bladder interface are the most reliable sonographic features at 11–14 weeks associated with subsequent diagnosis of PAS50. A recently published assessment of a two-stage screening and diagnostic protocol for CSP also demonstrated high accuracy for sonographic prediction of PAS in the first trimester (false-positive rate of 0.1%); in that study51, all cases of PAS were associated, at the time of diagnostic assessment as early as 12 weeks in a PAS-specialized clinic, with the sonographic features: intraplacental lacunae, retroplacental arterial-trophoblastic blood flow and irregular placental vascularization on three-dimensional power Doppler. These two studies50, 51 describe ‘classic’ ultrasound findings identified in the late first to early second trimesters for accurately characterizing PAS. We argue that, not only can predictions about PAS be made even sooner (in the early first trimester), but also, such evaluations should be performed routinely to improve patient outcome and expand management options. The same publications which have described several sonographic characteristics for accurate late first-trimester diagnosis of PAS have also demonstrated that cases which go on to develop PAS exhibit first-trimester sonographic characteristics similar to those of CSP50. Additionally, there is a well-documented histopathological connection between CSP and PAS, suggesting not only that these two entities are related fundamentally, but also that CSP is very frequently a precursor to PAS52, 53. Zosmer et al.47 studied several cases of women opting to manage expectantly their CSP, and described the natural course of these gestations: ‘Placenta previa and varying degrees of morbidly adherent placenta develop in all patients who continue the pregnancy.’. The presence of previa in the first trimester is rarely reported because it usually resolves in later trimesters; Hill et al.54 found that only 4.8% of cases of placenta previa detected in the first trimester persisted to term. However, previa in the setting of CSP is an entirely different scenario and frequently these abnormally implanted placentae not only fail to resolve, but also hint at underlying invasion51. Furthermore, one of the hallmark diagnostic findings for CSP, namely low anterior gestational sac position between 5 and 7 weeks, correlated 100% of the time with development of PAS41-43. Given this well-documented connection, we argue that CSP, which we know can be diagnosed accurately in the early first trimester, can itself serve as the sought-after early-pregnancy sonographic marker for predicting PAS. While not all CSP cases are ultimately diagnosed with PAS and labeling all CSP cases as ‘PAS until proven otherwise’ might result in false positives, it is important to remember that CSP alone is a fundamentally high-risk pregnancy; this risk is only compounded by the additional diagnosis of invasive placenta. Furthermore, the risk of not diagnosing CSP and/or PAS, thereby missing an opportunity for low-risk management due to a delay in diagnosis, arguably holds far graver consequences for patients than does a false-positive diagnosis in the early first trimester17. To quote El-Refaey et al.21, ‘All women with prior caesarean section should have a 6- to 8-week scan to predict placenta accreta.’. This concept was later developed in a systematic review by Gonzalez and Tulandi55, who stated: ‘Because early diagnosis and treatment are important for the best outcome, every pregnant woman with history of a cesarean delivery should be screened early in the first trimester of pregnancy to rule out this life-threatening complication. Diagnosis can be achieved with ultrasound and Doppler imaging.’. We believe that early diagnosis is paramount to improved patient outcome, and a component of this improvement is the opportunity for optimal management from earlier in gestation. CSP complications and untoward developments are directly correlated with the gestational age at which the CSP is diagnosed and treated, with later diagnosis carrying a higher risk of complications. For example, a study of excessive blood loss during suction evacuation treatment of CSP demonstrated a significant increase in risk of maternal hemorrhage with increasing gestational age, specifically greater than 8 weeks56. These temporal trends prompt us to advocate a TVS scan as early as possible during the first trimester (i.e. at 5–7 weeks), as ultrasound examination during this time span can reveal the location of the early gestational sac, the most reliable sign of a CSP, and potential placental implantation abnormalities. Figure 1 depicts the TVS markers of early first-trimester CSP. Figure 2 shows the ultrasound markers from 8 to 10 weeks. If, following evidence-based counseling, a patient makes the personal decision to terminate a CSP, the necessary procedure for terminating the pregnancy is time-sensitive. Thus, early and accurate diagnosis is paramount to facilitating timely management. At 5–6 weeks' gestation, a local intragestational methotrexate (MTX) or potassium chloride injection with adjuvant systemic administration of MTX or a single-/double-balloon treatment is a simple and effective management protocol for terminating early CSP57-59. Applied between 5 and 8 weeks, the minimally invasive double-balloon procedure has a low complication rate. Even a suction evacuation at 5–7 weeks can be performed relatively safely58. However, with every passing day that the accurate diagnosis and/or decision to terminate is delayed, the gestational sac, the embryo and, most importantly, its vascularization, are growing rapidly. Within days, what might have been a simple, uncomplicated termination can evolve into a much more complex procedure requiring more and greater and associated with higher risk of morbidity for the A of a of weeks example, weeks with 5–7 the of a usually an an and an It is documented in the literature that termination of CSP at or after weeks the rate of initial treatment and for more such as uterine artery and/or gravid all of which by their very higher risk for complications and even loss of (in cases of and accurate diagnosis is important after evidence-based counseling, a patient makes the decision to continue a CSP than terminating the In this obstetricians may the of a and the patient to a center that can provide as well as and care (in of are to manage PAS if this A recent systematic studies the of diagnosis of PAS on maternal outcome, with a diagnosis of invasive placenta] had blood loss during to the of blood to and to were in women with a diagnosis of invasive placenta] with in those with an It is from several published cases and clinical experience that the of an undiagnosed invasive placenta at the time of a even Cesarean section (or other surgical can have for described a of an Cesarean section complicated by undiagnosed PAS the which and While this may be an occurrence, most obstetricians can to such deliveries for the of their It is that such a scenario can be or avoided by of routine early first-trimester ultrasound examination after a previous Cesarean delivery. to the on of in screening as of or by the of or other which can be applied The various to the of a screening The for which screening is being considered should be an important with a or examination that is to the as well as an already diagnosis of the and administration of the treatment should be including the necessary to should be a or early of the and its natural including development from to should be also to be an agreed on to which into the the of including diagnosis and should be in to medical as a screening should be a not a and for the incidence of CSP is lower than that of other such as or pre-eclampsia, for which the of first-trimester screening is it a life-threatening with potentially devastating consequences. of cases at risk of CSP or would be to the high of maternal and morbidity associated with Furthermore, although not the natural history of CSP is Many CSPs present with and life-threatening such as hemorrhage or uterine which lead to while those progressing the first trimester evolve severe PAS of the CSP would treatment of the with improved maternal although a large variety of treatment for CSP have been reported in the published literature, termination of pregnancy in cases with heart beat the most because there is no reliable ultrasound sign with which to identify women who will experience severe symptoms in the first trimester of is the optimal approach in cases with no heart a reliable and which has been to identify accurately CSP and adverse in the early first assessment of the uterine scar in women with prior Cesarean section to many of required of a screening the and long-term impact on maternal of a screening for CSP should be first-trimester weeks of gestation) ultrasound assessment is not routinely in the majority of developed there are such as by techniques or previous ectopic pregnancy or CSP, and many medical that the first ultrasound assessment in pregnancy should be performed between and weeks of gestation. for CSP would the introduction of an additional ultrasound assessment, and its on for should be its in the outcome of these women. Furthermore, although reliable in ultrasound assessment of the scar after Cesarean section with to the modality and of diagnosis of CSP is well there is about how to identify and those cases not with the of CSP but implantation of the gestational sac between a prior Cesarean section scar and the uterine The introduction of ultrasound screening for CSP would an for and healthcare providers because imaging predict clinical outcome when CSP is detected in women. first-trimester such as hemorrhage or uterine the most likely clinical scenario for cases with heart the of progression severe but potentially such as PAS, the of how to these women and termination of pregnancy should the only treatment should focus on more accurate prediction that are to differentiate women at higher risk of first-trimester symptoms from those in which progression to although potentially complicated by PAS is more it should be that, as a result of the of one of the of this Opinion very early first-trimester sonography of pregnant patients with a history of previous Cesarean delivery has been into obstetrics and in this has not been into routine there is no established guideline for the of care and sonographic screening for related such as CSP and PAS. We the of not only the medical but also patients, about the of in early we have demonstrated that ultrasound is a accurate and reliable for the of first-trimester CSP and PAS in the of a anterior gestational and placenta previa in patients with one or more prior Cesarean Furthermore, the last two we have that new screening for adverse such as and have earlier and reductions in their should we not consider an earlier screening for CSP and PAS, that are potentially the potential for morbidity and even in these patients, early first-trimester (i.e. at 5–7 sonography of pregnant patients with a history of Cesarean section would be an addition to routine care that would be to and should be as as a in the of of care would be both and not only for the management available to patients, but also for their
Timor‐Tritsch et al. (Thu,) studied this question.