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      Management of Abnormal Placenta Implantation with Methotrexate: A Review of Published Data

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          Abstract

          Abnormally invasive placenta is characterized by direct attachment of chorionic villi to the uterine wall. This adherent placenta traditionally has been managed by peripartum hysterectomy. Nowadays, there is a lot of interest toward gradual shift from traditional management of invasive placentation to conservative ones leaving the placenta in situ to avoid the surgical morbidity of hysterectomy and loss of future fertility. Administration of methotrexate (MTX), as an adjunctive antimetabolite drug, resulted in conflicting data during conservative management of abnormal placentation. This review assessed all published data on efficacy and safety of MTX therapy as conservative management of invasive placentation. Fifty-three articles including one prospective cohort study, 2 retrospective cohort studies, 10 case series and 40 case reports were identified. Conservative management has beneficial effects on the avoidance of major surgery with the consequent morbidity and the preservation of future fertility. Infection and vaginal bleeding were main complications of MTX therapy. Although MTX therapy may result in accelerated involution or expulsion of placenta and has some beneficial effects on hemorrhagic events, but there is not enough evidence on its efficacy and safety to recommend its routine uses in all cases of invasive placenta.

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          Most cited references58

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          Clinical risk factors for placenta previa-placenta accreta.

          Our purpose was to define the clinical risk factors associated with placenta previa-placenta accreta. Hospital records were reviewed of all cases of placenta accreta confirmed histologically between January 1985 and December 1994. Additionally, we reviewed the records of all women with placenta previa and all those undergoing cesarean hysterectomy during the same period. Multiple logistic regression analysis was used to identify independent clinical risk factors for placenta accreta. Among 155,670 deliveries, 62 (1/2510) were complicated by histologically confirmed placenta accreta. Placenta accreta occurred in 55 of 590 (9.3%) women with placenta previa and in 7 of 155,080 (1/22,154) without placenta previa (relative risk 2065, 95% confidence interval 944 to 4516, p or = 35 years) and previous cesarean delivery were independent risk factors for placenta accreta. Placenta accreta was present in 36 of 124 (29%) cases in which the placenta was implanted over the uterine scar and in 4 of 62 (6.5%) cases in which it was not (relative risk 4.5, 95% confidence interval 1.68 to 12.07). Among women with placenta previa, the risk of placenta accreta ranged from 2% in women < 35 years old with no previous cesarean deliveries to almost 39% in women with two or more previous cesarean deliveries and an anterior or central placenta previa. Placenta accreta occurs in approximately 1 of 2500 deliveries. Among women with placenta previa, the incidence is nearly 10%. In this high-risk group advanced maternal age and previous cesarean section are independent risk factors.
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            The management of placenta percreta: conservative and operative strategies.

            Our purpose was to assess preferences for the management of placenta percreta and identify aspects of care related to an improved outcome. Both an analysis of a questionnaire issued to members of the Society of Perinatal Obstetricians and a retrospective study at our institution were used to obtain case histories of women with placenta percreta during a recent 3-year period. Fifty-five of the 109 cases (50%) reported by members of the Society of Perinatal Obstetricians were suspected ante partum. Complications associated with this disorder included uterine rupture (3 cases), transfusion of > 10 units (44 cases, 40%), ureteral ligation or fistula formation (5 cases each, 5%), infection (31 cases, 28%), perinatal death (10 cases, 9%), and maternal death (8 cases, 7%). Management options included surgical removal of the uterus and involved tissues (101 cases, 93%) and conservative treatment with the placenta left in situ after delivery (8 cases, 7%). More members of the Society of Perinatal Obstetricians responding to our survey opted for conservative management if adjacent tissues were involved (69% with extension into the bladder or gastrointestinal tract) compared with 31% when the percreta was confined to the uterus, p < 0.001. Conservative therapy was also associated with less blood loss in reported cases (median units red blood cells transfused, 0 vs 7, p = 0.003). Two of the three cases of placenta percreta at our institution were identified ante partum. The third case represents the first reported with antepartum identification of percreta followed by deliberate conservative treatment. With greater involvement of surrounding tissues, conservative treatment was preferred in hemodynamically stable patients. If surgical excision of the placenta is attempted or necessary, physicians experienced in pelvic dissection must be involved because of the frequency of maternal morbidity and mortality.
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              Maternal outcome after conservative treatment of placenta accreta.

              To estimate maternal outcome after conservative management of placenta accreta. This retrospective multicenter study sought to include all women treated conservatively for placenta accreta in tertiary university hospital centers in France from 1993 to 2007. Conservative management was defined by the obstetrician's decision to leave the placenta in situ, partially or totally, with no attempt to remove it forcibly. The primary outcome was success of conservative treatment, defined by uterine preservation. The secondary outcome was a composite measure of severe maternal morbidity including sepsis, septic shock, peritonitis, uterine necrosis, fistula, injury to adjacent organs, acute pulmonary edema, acute renal failure, deep vein thrombophlebitis or pulmonary embolism, or death. Of the 40 university hospitals that agreed to participate in this study, 25 institutions had used conservative treatment at least once (range 1-46) and had treated a total of 167 women. Conservative treatment was successful for 131 of the women (78.4%, 95% confidence interval [CI] 71.4-84.4%); of the remaining 36 women, 18 had primary hysterectomy and 18 had delayed hysterectomy (10.8% each, 95% CI 6.5-16.5%). Severe maternal morbidity occurred in 10 cases (6.0%, 95% CI 2.9-10.7%). One woman died of myelosuppression and nephrotoxicity related to intraumbilical methotrexate administration. Spontaneous placental resorption occurred in 87 of 116 cases (75.0%, 95% CI 66.1-82.6%), with a median delay from delivery of 13.5 weeks (range 4-60 weeks). Conservative treatment for placenta accreta can help women avoid hysterectomy and involves a low rate of severe maternal morbidity in centers with adequate equipment and resources.
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                Author and article information

                Journal
                GOI
                Gynecol Obstet Invest
                10.1159/issn.0378-7346
                Gynecologic and Obstetric Investigation
                Gynecol Obstet Invest
                S. Karger AG (Basel, Switzerland karger@ 123456karger.com http://www.karger.com )
                0378-7346
                1423-002X
                November 2016
                07 July 2016
                : 81
                : 6
                : 481-496
                Affiliations
                aDepartment of Clinical Pharmacy, Isfahan University of Medical Sciences, Isfahan, bDepartment of Clinical Pharmacy, Tehran University of Medical Sciences, cDepartment of Obstetrics and Gynecology, Firoozgar Hospital, and Department of Clinical Pharmacy, School of Pharmacy-International Campus, dDepartment of Clinical Pharmacy, School of Pharmacy-International Campus, FCRDC, Firoozgar Hospital, and eDepartment of Clinical Pharmacy, School of Pharmacy-International Campus, Colorectal Research Center (CRRC), Rasoul-e-Akram Hospital, Iran University of Medical Sciences, Tehran, Iran
                Article
                GOI2016081006481 Gynecol Obstet Invest 2016;81:481-496
                10.1159/000447556
                27384687
                e1db1b81-6292-4920-908c-3b18887b27b6
                © 2016 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                : 16 February 2016
                : 13 June 2016
                Page count
                Figures: 1, Tables: 1, References: 73, Pages: 16
                Categories
                Narrative Review

                Medicine,General social science
                Conservative management,Invasive placenta,Adherent placenta,Methotrexate

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