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Persistent retained placenta percreta: methotrexate treatment and Doppler flow characteristics
BJOG: an International Journal of Obstetrics and Gynaecology May 2002, Vol. 109, pp. 587 – 588
CASE REPORT
Persistent retained placenta percreta: methotrexate treatment and Doppler flow characteristics Remco G.W. Nijman*, Albert Mantingh, Jan G. Aarnoudse Case report A 38 year old woman was referred to the Academic Hospital Groningen because of a retained placenta that did not decrease in size after four weeks of conservative management. Her previous obstetric history revealed an ectopic pregnancy and uterine evacuation for a blighted ovum. Thirty-three days before admission she had an uncomplicated spontaneous vaginal delivery elsewhere after an uneventful pregnancy, followed by a retained placenta. An attempt to remove the placenta manually failed. Because she had no vaginal blood loss and her condition was haemodynamically stable, conservative management was planned. At admission 33 days postpartum, ultrasonography (ACUSON 128XP) showed a placenta (8 cm 6 cm) in utero, invading almost completely the myometrium of the uterine wall (Fig. 1a). Colour Doppler ultrasonography revealed blood flow in the spiral arteries into the intervillous space. The pulsatility index in the left and the right uterine artery was 0.67 and 0.79 (Fig. 1c), respectively, indicating a low vascular impedance and increased uteroplacental blood flow as is seen in the second half of pregnancy. Magnetic resonance imaging showed a transmural extension of the placenta throughout the uterus (percreta). Maternal serum alpha-fetoprotein was normal, but the serum human chorionic gonadotrophin (hCG) concentration was 330 iu/L. Our working diagnosis was persistent retained placenta increta or percreta and we decided to administer methotrexate intramuscular weekly (1 mg/kg). Four weeks after the methotrexate therapy was started, maternal serum hCG became undetectable (<5 iu/L), after four methotrexate injections (total dose 240 mg). The therapy was discontinued two weeks later.
Department of Obstetrics and Gynaecology, Academic Hospital Groningen, The Netherlands * Correspondence: Dr R. G. W. Nijman, Department of Obstetrics and Gynaecology, Medical Centre Leeuwardenm, Mr P. J. Troelstraweg 78, 8917 CR Leeuwarden, The Netherlands. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S 1 4 7 0 - 0 3 2 8 ( 0 2 ) 0 1 0 4 0 - 6
We assessed weekly the patient’s haemoglobin concentration, the leucocyte and platelet counts and the liver and kidney function tests during the course of treatment; all values remained within the normal range. Doppler measurements were performed weekly after methotrexate treatment was started and monthly when the therapy was discontinued. The volume of the placenta showed a slight decrease in size after the first week, and a more rapid decrease after two injections of methotrexate. A small, but highly echodense spot of 1 cm – 2 cm persisted in the left fundal area 170 days postpartum (Fig. 1b); serum hCG remained undetectable and the velocity waveform of the uterine arteries had returned to a normal non-pregnant pattern (Fig. 1d).
Discussion There are three varieties of placenta accreta: placenta accreta in which there is no dividing line between the decidua compacta and decidua spongiosa, nor can the operator establish any line of cleavage between the placenta and uterine wall; placenta increta in which the chorionic villi make contact with, but do not invade the myometrium; placenta percreta in which the whole thickness of the myometrium is invaded to the serosal surface with possibility of rupture into the peritoneal cavity. Known risk factors are: 1. manual removal of placenta at a previous birth; 2. vigorous and repeated curettage; 3. presence of submucous fibroids, with subsequent atrophy of the overlying mucosa; 4. placenta praevia; 5. pregnancy in an uterine diverticulum; 6. previous caesarean section scar; and 7. after previous treatment by radioactive radium. Maternal and perinatal morbidity is common in pregnancies with placenta percreta due to uterine rupture, blood loss, ureteral ligation in pregnancies, fistula formation or infection. The options for treatment include surgical removal of the uterus or conservative treatment with the placenta left in situ. In the literature seven cases have been reported of conservative treatment of placenta accreta or percreta with methotrexate1. Uterine artery Doppler flow measurements under these circumstances have not been reported so far. www.bjog-elsevier.com
588
CASE REPORT
Fig. 1. (A) Persistent retained placenta percreta, 33 days postpartum; (B) uterine cavity after methotrexate therapy, 170 days postpartum; (C) pulsatility index of the left uterine artery, 33 days postpartum; (D) pulsatility index of the left uterine artery after methotrexate therapy, 170 days postpartum.
The persistent low impedance in the uterine arteries that we found is most likely the result of an enduring uteroplacental circulation postpartum supplying the viable placental tissue. Several studies have pointed out that normally the systolic:diastolic ratio of the uterine arteries significantly increases the first month postpartum2,3. We decided to start treatment with methotrexate because of the persistent retained placenta with a low pulsatility index of the uterine arteries and increased serum hCG. The literature states that even in cases of an undetectable hCGlevel, methotrexate can successfully cure persistent retained placental tissue. It is suggested that methotrexate acts not only on the dividing trophoblast cells but has effects on neovascularisation and growth factors as well3. Methotrexate has been shown to decrease trophoblast activity and to reduce placental vascularity4. After treatment with methotrexate, the placental size, which was weekly assessed ultrasonographically, reduced rapidly. After four courses we could hardly detect any trophoblastic tissue and the pulsatility index of the uterine arteries had increased to non-pregnant values, including an early diastolic notch.
Our case demonstrates that conservative treatment of persistent retained placenta percreta can be successful. In our case, we observed that methotrexate administration resulted in a decrease of uteroplacental blood flow accompanied by reduction of placental size, eventually resulting in disappearance of the placenta.
References 1. Gupta D, Sinha R. Management of placenta accreta with oral methotrexate. Int J Gynaecol Obstet 1998;60:171 – 173. 2. Reles A, Ertan AK, Kainer F, Dudenhausen JW. Dopplersonographische Befunde der Arteria uterina und Uterusinvolution im normalen Puerperium [German]. Gynakol Geburtshilfliche Rundsch 1992; 32:66 – 72. 3. Kirkinen P, Dudenhausen J, Baumann H, Huch R. Postpartum blood flow velocity waveforms of the uterine arteries. J Reprod Med 1988; 33:745 – 748. 4. Flam F, Karlstroˆm FP-O, Carlsson B, Garoff L. Methotrexate for retained placental tissue. Eur J Obstet Gynecol Reprod Biol 1999; 83:127 – 129. Accepted 31 July 2001
D RCOG 2002 Br J Obstet Gynaecol 109, pp. 587 – 588
CASE REPORT
Persistent retained placenta percreta: methotrexate treatment and Doppler flow characteristics Remco G.W. Nijman*, Albert Mantingh, Jan G. Aarnoudse Case report A 38 year old woman was referred to the Academic Hospital Groningen because of a retained placenta that did not decrease in size after four weeks of conservative management. Her previous obstetric history revealed an ectopic pregnancy and uterine evacuation for a blighted ovum. Thirty-three days before admission she had an uncomplicated spontaneous vaginal delivery elsewhere after an uneventful pregnancy, followed by a retained placenta. An attempt to remove the placenta manually failed. Because she had no vaginal blood loss and her condition was haemodynamically stable, conservative management was planned. At admission 33 days postpartum, ultrasonography (ACUSON 128XP) showed a placenta (8 cm 6 cm) in utero, invading almost completely the myometrium of the uterine wall (Fig. 1a). Colour Doppler ultrasonography revealed blood flow in the spiral arteries into the intervillous space. The pulsatility index in the left and the right uterine artery was 0.67 and 0.79 (Fig. 1c), respectively, indicating a low vascular impedance and increased uteroplacental blood flow as is seen in the second half of pregnancy. Magnetic resonance imaging showed a transmural extension of the placenta throughout the uterus (percreta). Maternal serum alpha-fetoprotein was normal, but the serum human chorionic gonadotrophin (hCG) concentration was 330 iu/L. Our working diagnosis was persistent retained placenta increta or percreta and we decided to administer methotrexate intramuscular weekly (1 mg/kg). Four weeks after the methotrexate therapy was started, maternal serum hCG became undetectable (<5 iu/L), after four methotrexate injections (total dose 240 mg). The therapy was discontinued two weeks later.
Department of Obstetrics and Gynaecology, Academic Hospital Groningen, The Netherlands * Correspondence: Dr R. G. W. Nijman, Department of Obstetrics and Gynaecology, Medical Centre Leeuwardenm, Mr P. J. Troelstraweg 78, 8917 CR Leeuwarden, The Netherlands. D RCOG 2002 BJOG: an International Journal of Obstetrics and Gynaecology PII: S 1 4 7 0 - 0 3 2 8 ( 0 2 ) 0 1 0 4 0 - 6
We assessed weekly the patient’s haemoglobin concentration, the leucocyte and platelet counts and the liver and kidney function tests during the course of treatment; all values remained within the normal range. Doppler measurements were performed weekly after methotrexate treatment was started and monthly when the therapy was discontinued. The volume of the placenta showed a slight decrease in size after the first week, and a more rapid decrease after two injections of methotrexate. A small, but highly echodense spot of 1 cm – 2 cm persisted in the left fundal area 170 days postpartum (Fig. 1b); serum hCG remained undetectable and the velocity waveform of the uterine arteries had returned to a normal non-pregnant pattern (Fig. 1d).
Discussion There are three varieties of placenta accreta: placenta accreta in which there is no dividing line between the decidua compacta and decidua spongiosa, nor can the operator establish any line of cleavage between the placenta and uterine wall; placenta increta in which the chorionic villi make contact with, but do not invade the myometrium; placenta percreta in which the whole thickness of the myometrium is invaded to the serosal surface with possibility of rupture into the peritoneal cavity. Known risk factors are: 1. manual removal of placenta at a previous birth; 2. vigorous and repeated curettage; 3. presence of submucous fibroids, with subsequent atrophy of the overlying mucosa; 4. placenta praevia; 5. pregnancy in an uterine diverticulum; 6. previous caesarean section scar; and 7. after previous treatment by radioactive radium. Maternal and perinatal morbidity is common in pregnancies with placenta percreta due to uterine rupture, blood loss, ureteral ligation in pregnancies, fistula formation or infection. The options for treatment include surgical removal of the uterus or conservative treatment with the placenta left in situ. In the literature seven cases have been reported of conservative treatment of placenta accreta or percreta with methotrexate1. Uterine artery Doppler flow measurements under these circumstances have not been reported so far. www.bjog-elsevier.com
588
CASE REPORT
Fig. 1. (A) Persistent retained placenta percreta, 33 days postpartum; (B) uterine cavity after methotrexate therapy, 170 days postpartum; (C) pulsatility index of the left uterine artery, 33 days postpartum; (D) pulsatility index of the left uterine artery after methotrexate therapy, 170 days postpartum.
The persistent low impedance in the uterine arteries that we found is most likely the result of an enduring uteroplacental circulation postpartum supplying the viable placental tissue. Several studies have pointed out that normally the systolic:diastolic ratio of the uterine arteries significantly increases the first month postpartum2,3. We decided to start treatment with methotrexate because of the persistent retained placenta with a low pulsatility index of the uterine arteries and increased serum hCG. The literature states that even in cases of an undetectable hCGlevel, methotrexate can successfully cure persistent retained placental tissue. It is suggested that methotrexate acts not only on the dividing trophoblast cells but has effects on neovascularisation and growth factors as well3. Methotrexate has been shown to decrease trophoblast activity and to reduce placental vascularity4. After treatment with methotrexate, the placental size, which was weekly assessed ultrasonographically, reduced rapidly. After four courses we could hardly detect any trophoblastic tissue and the pulsatility index of the uterine arteries had increased to non-pregnant values, including an early diastolic notch.
Our case demonstrates that conservative treatment of persistent retained placenta percreta can be successful. In our case, we observed that methotrexate administration resulted in a decrease of uteroplacental blood flow accompanied by reduction of placental size, eventually resulting in disappearance of the placenta.
References 1. Gupta D, Sinha R. Management of placenta accreta with oral methotrexate. Int J Gynaecol Obstet 1998;60:171 – 173. 2. Reles A, Ertan AK, Kainer F, Dudenhausen JW. Dopplersonographische Befunde der Arteria uterina und Uterusinvolution im normalen Puerperium [German]. Gynakol Geburtshilfliche Rundsch 1992; 32:66 – 72. 3. Kirkinen P, Dudenhausen J, Baumann H, Huch R. Postpartum blood flow velocity waveforms of the uterine arteries. J Reprod Med 1988; 33:745 – 748. 4. Flam F, Karlstroˆm FP-O, Carlsson B, Garoff L. Methotrexate for retained placental tissue. Eur J Obstet Gynecol Reprod Biol 1999; 83:127 – 129. Accepted 31 July 2001
D RCOG 2002 Br J Obstet Gynaecol 109, pp. 587 – 588