Over the last century, the incidence of placenta accreta, increta, and percreta, collectively referred to as morbidly adherent placenta, has risen dramatically. Planned cesarean hysterectomy at the time of cesarean delivery is the standard recommended treatment in the United States. Recently, interest in conservative management has resurged, especially in Europe. The aims of this review are the following: (1) to provide an overview of methods used for conservative management, (2) to discuss clinical implications for both clinicians and patients, and (3) to identify areas in need of further research.
Morbidly adherent placenta (MAP) includes the spectrum of placenta accreta, increta, and percreta and is a cause of major morbidity and mortality in pregnant women. Abnormal vascularization results from the scarring process following uterine surgery with secondary localized hypoxia, leading to defective decidualization and excessive trophoblastic invasion.
In the last century, the incidence of MAP has risen from approximately 1 in 20,000 live births in 1928 to a rate of 1 in 533 in 2002. Per a 2012 population-based study from the United Kingdom, this rate may be as low as 1.7 in 10,000 pregnancies overall but as high as 1 in 20 pregnancies in women with both placenta previa and a prior cesarean delivery. MAP is associated with massive hemorrhage, especially with extirpative or forcible attempts at placental removal. Actual maternal mortality risk is unknown but has been reported to be as high as 6-7%, possibly higher in developing regions.
Antenatal diagnosis and delivery by cesarean hysterectomy between 34 and 35 weeks gestation by experienced, multidisciplinary teams reduce the risk of morbidity and mortality. In a retrospective study from Finland of 44 cases of morbidly adherent placenta diagnosed either antenatally or at the time of delivery, the median estimated blood loss was 4500 mL (range, 100–15,000 mL) when an antenatal diagnosis was suspected, compared with 7800 mL (range, 2500–17,000 mL). Women with an antenatal diagnosis required a median of 7 U of packed red blood cells (range, 0–27 U), compared with 13.5 U (range, 4–31 U) when MAP was diagnosed at delivery.
Similar findings were reported by Fitzpatrick et al, in a retrospective cohort of 134 cases of MAP identified by the United Kingdom Obstetrical Surveillance System, which surveys 221 hospitals across the United Kingdom. The authors reported an estimated blood loss of greater than 2500 mL in 36–40% of patients. Transfusion was required in 59% of the women with placenta increta or percreta diagnosed antenatally compared with 94% of women with an intrapartum diagnosis of increta or percreta.
In these studies, antenatal diagnosis was made in approximately 50% of cases, which is consistent with data from a 2015 retrospective cohort from the Eunice Kennedy Shriver National Institute of Child Health and Disease Maternal-Fetal Medicine Units Network analysis of the Assessment of Perinatal Execllence database of deliveries from 25 hospitals across the United States. These data reflect antenatal diagnoses from both referral centers and community hospitals and are perhaps more generalizable than the higher rates of antenatal diagnosis reported from large tertiary referral centers.
Surgical principles include avoiding disruption of the hypervascular placenta, stepwise devascularization, early and comprehensive blood product transfusion, and judicious use of interventional radiologic techniques such as vascular embolization.
Conservative management describes any approach whereby hysterectomy is avoided. It is utilized when the intraoperative findings suggest that hysterectomy carries an unacceptably high risk of hemorrhage or adjacent tissue injury that may be mitigated by leaving the placenta in situ. Uterine preservation may be attractive to women who desire future child-bearing or whose fertility is inextricably linked with societal status and self-esteem. Some authors endorse conservative management for highly motivated, appropriately counseled women who are willing to adhere to close follow-up in centers equipped to manage potential complications.
We aim to provide an overview of conservative management approaches, discuss implications for both physicians and patients, and identify areas for future research.
Uterine-sparing techniques
Leaving the placenta in situ: expectant management
The earliest described conservative technique is a hands-off approach, whereby the umbilical cord is ligated close to its placental insertion after delivery without any attempt to remove the placenta. Contemporary expectant management includes the use of adjunctive measures to reduce blood loss and expedite placental resorption. The placenta is left in situ after high ligation of the cord, with all or part of the placenta remaining adherent to the myometrium. After a cesarean delivery, the hysterotomy is closed in the routine fashion. Uterotonics, compression sutures, balloon tamponade, uterine artery embolization, and/or uterine artery ligation may reduce uterine perfusion, decrease postpartum hemorrhage, and hasten placental resorption or sloughing and expulsion.
The time to a spontaneous resolution ranges from 4 weeks to 9-12 months, with a mean of 6 months. Delayed hemorrhage, disseminated intravascular coagulopathy, endomyometritis, and sepsis were reported as major complications of placental retention. Rare morbidities included uterocutaneous fistula and choriocarcinoma with arteriovenus fistula formation.
In one of the largest retrospective reviews (n = 167), Sentilhes et al reported that 78% of women retained their uterus. More than half (52%) were given postpartum prophylactic antibiotics over 5 days. A majority (65%) required additional procedures, including pelvic artery embolization (n = 62), hypogastric artery ligation (n = 23), other vessel ligation (n = 45), and uterine compression sutures (n = 16). Half (51%) had postpartum hemorrhage, and 36 of those (22%) required subsequent hysterectomy (18 within 24 hours, 18 within 3 months of delivery). When successful, resolution occurred at a median of 13.5 weeks’ postpartum. Ten patients suffered severe morbidity, including septic shock, vesicouterine fistula, and uterine necrosis. There was 1 maternal death associated with complications following the use of methotrexate.
More than half of the previously mentioned cases (55%) had no diagnostic imaging. Only 18 patients had placenta percreta and histological confirmation of the depth of invasion was available only when hysterectomy was performed. This raises the question of bias toward cases involving only partial or focal involvement.
Pather et al reviewed 57 cases of placenta percreta that were diagnosed by antenatal imaging and managed conservatively. They showed that 60% of patients required further surgery (40% as emergent hysterectomy) and that up to 42% experienced major morbidity including sepsis, disseminated intravascular coagulopathy, hemorrhage, pulmonary embolism, and fistula and arteriovenus malformation.
Clausen et al systematically reviewed 52 studies involving 119 cases of placenta percreta diagnosed by antenatal imaging or at the time of delivery. Of these, 36 cases were managed by leaving the placenta in situ and were associated with hemorrhage, infection, and a 58% risk of delayed hysterectomy as late as 9 months after the delivery, emergently 85% of the time.
Hysteroscopic resection of retained adherent placenta
Hysteroscopic resection of placental remnants has been described to expedite resolution or treat delayed bleeding and/or pelvic pain. Potential advantages of using a hysteroscopic approach include the ability to visually confirm absence of a cleavage plane, continually visualize tissues during resection, and reduce risk of adhesion formation.
In 1 series, 4 women who were managed conservatively underwent hysteroscopy caused by severe pain, at a mean of 209 days (range, 65–362 days). Pain resolved within 1 week of the procedure. Two of the 4 subsequently conceived and delivered via cesarean delivery, with no evidence of recurrence of placenta accreta.
In a second series, 12 women underwent hysteroscopic resection of retained accreta using bipolar cautery with ultrasound guidance. Complete resolution occurred after a single procedure in 5 patients (42%), after 2 attempts in 2 patients (17%), and after 3 attempts in 4 patients (30%). One required hysterectomy because of a hemorrhage after the first resection. Nine patients had a return of menses after treatment, and in 4 subsequent pregnancies, there were 2 live births. It is important to note that in this series, the mean size of retained tissue (not defined clearly as length, width, or depth) was only 54 mm on magnetic resonance imaging (range, 13–110 mm). Median time from delivery to first resection was 75 days (range, 51–179 days). Pathological examination confirmed accreta in all cases.
Prior to hysteroscopic resection, the depth of placental invasion must be considered. Concurrent use of ultrasound or laparoscopic guidance is prudent to avoid inadvertent injury. There is no evidence to suggest that patients with placenta increta or percreta are candidates for hysteroscopic resection.
Placental-myometrial en bloc excision and repair
En bloc resection of placenta percreta was first described by Palacios et al, in 2004, in a series of 68 cases. This technique permitted resection of invaded myometrium when 50% or less of the anterior uterine circumference was involved. An important proviso is that bleeding had to be controlled by dissection and ligation of any neovascularization. Complete placental excision was performed after delivery of the fetus. Fibrin glue, uterine artery ligation, and brace or box sutures were used for local hemostasis. After excision, the resulting defect in the myometrium was repaired with myometrial pulley sutures, similar to horizontal mattress sutures. The defect was then covered with absorbable mesh. Uterine conservation was completed in 50 of the 68 women (74%). Of these, 42 had 3 year follow-up, and 10 became pregnant and were delivered at 36 weeks by scheduled cesarean delivery. Even with this technique, 18 of 68 patients (26%) still required hysterectomy, and adequate long-term data about the safety of pregnancy or subsequent surgery after use of mesh are lacking.
Chandraharan et al described the Triple P procedure in 2006 in a case series of 4 patients with central, anterior placenta percreta. This procedure involves 3 steps: (1) preoperative placental localization using transabdominal ultrasound to identify the superior border of the placenta, with transverse hysterotomy planned 2 fingerbreadths above the uppermost placental edge; (2) preoperative placement of intraarterial balloon catheters with inflation after delivery or ligation of the uterine arteries when catheterization is unavailable; and (3) no attempt to remove the placenta with en bloc myometrial excision and uterine repair. During the excision, a 2 cm margin of myometrium is preserved above the bladder edge to allow hysterotomy closure.
In cases involving bladder invasion or low-lying placenta, hemostatic clamps are placed along the incision edges, the lower segment is everted, placental fragments are removed piecemeal, and compression sutures are placed as needed for hemostasis. The resulting myometrial defect is then closed in the same way as a hysterotomy made at the time of cesarean delivery. All patients opted for bilateral tubal ligation at the time of delivery; thus, no follow-up data with regard to subsequent pregnancy are available.
The authors reported remarkably low blood loss, ranging from 800 to 1500 mL per patient. A follow-up cohort study by the same group showed reduction in estimated blood loss, the need for delayed hysterectomy, and length of inpatient stay when compared with leaving the placenta in situ plus arterial occlusion. The potential benefit of this procedure, in appropriately selected patients, may be in minimizing the surgical dissection necessary to attain adequate hemostasis while removing all or most of the placenta. The authors stated that lateral extension of a percreta into the broad ligaments, or deep infiltration into the cervix or the ureters, preclude safe employment of this technique.
Clausen et al reported 17 cases of placenta percreta treated with balloon occlusion and either hysterectomy or local resection. Mean estimated blood loss was lower in 9 patients in whom en bloc resection of the percreta was successful (2770 mL; range, 1300–6000 mL), compared with 8 women who underwent hysterectomy (5490 mL; range, 450–16,000 mL). The authors attributed the markedly higher blood loss in a single patient (16,000 mL) to extensive bladder adhesions and failure of timely inflation of an occlusion balloon. Even excluding this patient, the mean estimated blood loss and transfusion requirements remained higher in the hysterectomy group compared with the local resection group (3985 mL vs 2770 mL estimated blood loss; 1792 mL vs 1078 mL packed red blood cells transfused). Local resection relies heavily on the need for uterine artery occlusion, the utility of which remains controversial.
Adjunctive procedures
Arterial occlusion
Two primary methods of uterine artery occlusion have been described to reduce blood loss in cases of MAP: temporary use of intraarterial balloon catheters and uterine artery embolization. In the cohort study by Clausen et al noted in the previous text, 15 of 17 women had balloon occlusion catheters placed as part of a local protocol. It is important to note that the patient with the lowest estimated blood loss in this cohort underwent hysterectomy, and was one in whom balloon catheters were not placed. The authors noted only a “small change in bleeding when balloons were inflated in the internal iliac arteries.” This may be due to rich collateral feeding vessels arising from cervicovaginal branches of the uterine arteries, superior vesical, inferior epigastric, or femoral and deep circumflex iliac arteries.
Routine intravascular occlusion remains controversial because of the lack of adequately powered randomized clinical trials demonstrating benefit. The contribution toward hemostasis that can be attributed to intraarterial occlusion is also difficult to evaluate because it is seldom used in isolation. Reported complications include iliac thrombosis, inadvertent embolization of the external iliac arteries, uterine necrosis, leg ischemia, and necrosis of the buttocks.
Methotrexate
The use of methotrexate in the management of placenta accreta was first described in 1986. Methotrexate is a dihydrofolate reductase inhibitor that targets rapidly dividing cells, most commonly for the treatment of ectopic pregnancy and gestational trophoblastic disease. Some experts have used methotrexate as an adjunct to conservative management of placenta accreta ; however, the decrease in placental cell division in the third trimester limits the biological plausibility of purported benefits.
Some authors suggest that methotrexate is associated with rapid placental expulsion, yet there is significant overlap in the time to resolution with or without its use, and outcomes do not appear to differ significantly. Methotrexate is contraindicated during breast-feeding, which is widely accepted to promote neonatal short- and long-term health outcomes, maternal bonding, and neonatal attachment and may mitigate the risk of postpartum depression or perceived stress related to a traumatic delivery. Notably, the authors reporting the largest cohort of conservatively managed patients commented that “no convincing evidence currently supports the efficacy of methotrexate in cases of placenta accreta left in situ, and methotrexate-related pancytopenia and nephrotoxicity are possible adverse effects.”
Delayed hysterectomy
Delayed hysterectomy is largely described as an emergent procedure performed as a consequence of delayed complications after attempted conservative management. Planned delayed hysterectomy is not truly a conservative approach in the sense of being a fertility- or uterus-sparing method. Rather, it is a hybrid approach aimed at the prevention of complications that may occur with either immediate hysterectomy or prolonged placental retention. By allowing spontaneous regression of some of the placental bulk, it is believed that the risk of hemorrhage at the time of hysterectomy can be reduced. Published data to support this practice are scarce, and the optimal timing of planned delayed hysterectomy is unclear.
Adjunctive procedures
Arterial occlusion
Two primary methods of uterine artery occlusion have been described to reduce blood loss in cases of MAP: temporary use of intraarterial balloon catheters and uterine artery embolization. In the cohort study by Clausen et al noted in the previous text, 15 of 17 women had balloon occlusion catheters placed as part of a local protocol. It is important to note that the patient with the lowest estimated blood loss in this cohort underwent hysterectomy, and was one in whom balloon catheters were not placed. The authors noted only a “small change in bleeding when balloons were inflated in the internal iliac arteries.” This may be due to rich collateral feeding vessels arising from cervicovaginal branches of the uterine arteries, superior vesical, inferior epigastric, or femoral and deep circumflex iliac arteries.
Routine intravascular occlusion remains controversial because of the lack of adequately powered randomized clinical trials demonstrating benefit. The contribution toward hemostasis that can be attributed to intraarterial occlusion is also difficult to evaluate because it is seldom used in isolation. Reported complications include iliac thrombosis, inadvertent embolization of the external iliac arteries, uterine necrosis, leg ischemia, and necrosis of the buttocks.
Methotrexate
The use of methotrexate in the management of placenta accreta was first described in 1986. Methotrexate is a dihydrofolate reductase inhibitor that targets rapidly dividing cells, most commonly for the treatment of ectopic pregnancy and gestational trophoblastic disease. Some experts have used methotrexate as an adjunct to conservative management of placenta accreta ; however, the decrease in placental cell division in the third trimester limits the biological plausibility of purported benefits.
Some authors suggest that methotrexate is associated with rapid placental expulsion, yet there is significant overlap in the time to resolution with or without its use, and outcomes do not appear to differ significantly. Methotrexate is contraindicated during breast-feeding, which is widely accepted to promote neonatal short- and long-term health outcomes, maternal bonding, and neonatal attachment and may mitigate the risk of postpartum depression or perceived stress related to a traumatic delivery. Notably, the authors reporting the largest cohort of conservatively managed patients commented that “no convincing evidence currently supports the efficacy of methotrexate in cases of placenta accreta left in situ, and methotrexate-related pancytopenia and nephrotoxicity are possible adverse effects.”
Delayed hysterectomy
Delayed hysterectomy is largely described as an emergent procedure performed as a consequence of delayed complications after attempted conservative management. Planned delayed hysterectomy is not truly a conservative approach in the sense of being a fertility- or uterus-sparing method. Rather, it is a hybrid approach aimed at the prevention of complications that may occur with either immediate hysterectomy or prolonged placental retention. By allowing spontaneous regression of some of the placental bulk, it is believed that the risk of hemorrhage at the time of hysterectomy can be reduced. Published data to support this practice are scarce, and the optimal timing of planned delayed hysterectomy is unclear.
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