Journal of Obstetrics and Gynaecology
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of nonruptured interstitial pregnancy A. Pellegrino, G. R. Damiani, S. Landi, M. Tartagni, S. Tafuri, A. Caringella, C. Sportelli, M. Gaetani & G. Loverro To cite this article: A. Pellegrino, G. R. Damiani, S. Landi, M. Tartagni, S. Tafuri, A. Caringella, C. Sportelli, M. Gaetani & G. Loverro (2014) Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of non-ruptured interstitial pregnancy, Journal of Obstetrics and Gynaecology, 34:1, 93-95 To link to this article: http://dx.doi.org/10.3109/01443615.2013.789834
Published online: 20 Dec 2013.
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Obstetric Case Reports 93 Deans R, Abbott J. 2010. Hysteroscopic management of cesarean scar ectopic pregnancy. Fertility and Sterility 93:1735–1740. Jurkovic D, Hillaby K, Woelfer B et al. 2003. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. Ultrasound in Obstetrics and Gynecology 21:220–227. Maymon R, Halperin R, Mendlovic S et al. 2004. Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre. Human Reproduction 19:278–284. Rotas MA, Haberman S, Levgur M. 2006. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstetrics and Gynecology 107: 1373–1381. Seow KM, Huang LW, Lin YH et al. 2004. Cesarean scar pregnancy: issues in management. Ultrasound in Obstetrics and Gynecology 23:247–253. Shih JC. 2004. Cesarean scar pregnancy: diagnosis with three-dimensional (3D) ultrasound and 3D power Doppler. Ultrasound in Obstetrics and Gynecology 23:306–307. Tagore S, Teo SH, Chua SY et al. 2010. A retrospective review of uterine scar pregnancies: single centre experience. Archives of Gynecology and Obstetrics 282:711–715. Vial Y, Petignat P, Hohlfeld P. 2000. Pregnancy in a cesarean scar. Ultrasound in Obstetrics and Gynecology 16:592–593. Wang YL, Su TH, Chen HS. 2006. Operative laparoscopy for unruptured ectopic pregnancy in a caesarean scar. British Journal of Obstetrics and Gynaecology 113:1035–1038.
Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of non-ruptured interstitial pregnancy A. Pellegrino1, G. R. Damiani1, S. Landi2, M. Tartagni3, S. Tafuri4, A. Caringella3, C. Sportelli5, M. Gaetani3 & G. Loverro3 Department of Obstetrics and Gynecology, 1Malzoni Hospital, Lecco, 2Sondrio Hospital, Sondrio, 3University of Bari, Policlinico 4Department of Biomedical Sciences, Section of Hygiene, ‘Aldo Moro’ University, Bari and 5Alessandro Manzoni Hospital, Lecco, Italy DOI: 10.3109/01443615.2013.789834 Correspondence: G. R. Damiani, Department of Obstetrics and Gynecology, Malzoni Hospital, Lecco, Italy. E-mail: [email protected]
We report the efficacy of a minimally invasive approach of the multidose protocol with methotrexate (MTX) in the management of three cases of interstitial pregnancy (IP), with elevated serum b-hCG in two cases. New considerations and management strategies are discussed. Successful termination of IP and in one case, a subsequent successful pregnancy, was achieved. The process led to the development of an enhanced understanding of diagnostic modalities and their limitations, with regard to the particular entities under discussion. We also focused attention on pivotal points and anatomical features in the management of this dangerous occurrence. Long-term results with careful follow-up were analysed by instrumental procedure. This hazardous type of ectopic pregnancy can be managed with systemic administration of MTX, also in patients with elevated β-hCG values. The present report underlines that an integrated approach in early diagnosis, multidose treatment and close follow-up, are essential forms of medical management. Keywords: Cornual pregnancy, fallopian tube, interstitial pregnancy, methotrexate, multidose protocol
Introduction Interstitial pregnancy (IP) accounts for 2–4% of tubal pregnancies and is an ectopic pregnancy located outside of the uterine cavity, in the first part of the fallopian tube, surrounded by the muscular layer of the uterus, which allows a significant expansion when it hosts a pregnancy, but delays the clinical symptoms characterised
by heavy haemorrhage and high mortality rate (2.5%) (Damario and Rock 2003; Moawad et al. 2010; Tulandi and Al-Jaroudi 2004; Walsen 1957). Early diagnosis is mandatory in order to avoid massive transfusions and detrimental effects of surgery on future fertility, like cornual wedge resection or total hysterectomy (Walker 2007). The choice of treatment is still under discussion, although preliminary data revealed that medical treatment with methotrexate (MTX) is the gold standard, as in other ectopic pregnancies (Stovall and Ling 1993).
Case report 1 A 39-year-old nulliparous primigravida, presented to our institution with 7 weeks’ amenorrhoea, with recurrent vaginal bleeding lasting for 1 week. The β-hCG value was 8,166 mUI/ml, rising to 8,971 mUI/ml after 48 h. A transvaginal scanning revealed a 23 mm gestational sac at the right superolateral portion of the uterus, corresponding to 5 weeks’ gestational age, with no signs of embryonic viability, surrounded by a thin myometrium (⬍ 5 mm), outside of the empty uterine cavity and the interstitial line sign (Figure 1). These parameters have been interpreted as suggestive of an IP. Colour Doppler evidenced rich blood flow, with an image of a ring of fire, surrounding the sac and spectral tracing revealed a low resistance pattern, characteristic of trophoblastic blood flow (Figure 2). The patient was counselled about the ectopic implantation, the associated risks and all putative treatment regimens. Considering the rising levels of β-hCG and the patient’s desire to preserve fertility, systemic MTX administration was performed, at the dose of 1 mg/kg plus folinic acid 0, 1 mg/kg on days 0,2,4,6. Close follow-up was made, monitoring β-hCG and with ultrasound. The significant decline in the levels of β-hCG was observed from the 6th to 7th day onwards (Figure 3). Ultrasound monitoring revealed a gradual reduction in the size of the ectopic gestation from 24 mm to 16 mm, with a significant synchronous reduction of blood supply on the 8th day of MTX administration (Figure 4). The β-hCG fell gradually to non-pregnant levels within 36 days. After 6 months, hysteroscopy revealed a normal uterine cavity. A normal pregnancy occurred after 8 months, ending with a caesarean section for fetal distress.
Case report 2 A 37-year-old nulliparous woman, with 9 weeks’ amenorrhoea, presented to us complaining of vaginal spotting and acute abdominal pain. A transvaginal scan showed an eccentrically gestational sac of 29 mm, with embryonic viability, located at the outer right angle of fibromatous uterus. The pregnancy appeared implanted on the right extremity, where no myomas were present. The site of the gestational sac and the presence of the interstitial line sign suggested IP. The initial β-hCG value was 24, 213 mIU/l. MTX multidose protocol was administered as described above. On the 4th day, the β-hCG value was 16, 600 mIU/l, at the end of treatment on the 8th day 12, 1,312 mIU/l (Figure 5). Ultrasounds were performed on days 2, 5, 10 and then weekly until the risk of rupture, due to persistent trophoblastic proliferation, was presumed to disappear. This risk was evaluated by Doppler flow persistence in implantation site, which disappeared after 10 days from the beginning of treatment when the β-hCG level was 14.181 mIU/l. Ultrasound confirmed the resolution of the ectopic mass, 15 days after the termination of treatment.
Case report 3 A 33-year-old nulliparous woman with 7 weeks’ amenorrhoea, after a successful cycle of IVF, presented in our institution for vaginal bleeding. Ultrasonography revealed a singleton gestation, eccentrically placed in the left utero-tubal junctional area, lying 1 cm outside the most upper lateral edge of the decidualised cavity, measuring 0.4 cm. No embryo was visualised. Spectral tracing revealed a low resistant pattern deriving from trophoblastic tissue. The initial β-hCG was 1,351 mIU/l. Multidose protocol was administered. On the 8th day, β-hCG was 1,451 mIU/l, after 1 week 115 mIU/l and after another 5 days, the β-hCG level fell to 3 mIU/l.
Discussion The surrounding muscular wall of the interstitial portion confers ability to expand higher than other parts of fallopian tube.
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Figure 1. 3D-transvaginal scan revealed a small gestational sac (GS) at right superolateral portion of the uterus, surrounded by a thin myometrium (⬍ 5 mm), outside of the empty uterine cavity and the interstitial line sign (I.L.).
Therefore, the rupture is more delayed if compared with other portions, although IP is accompanied by a more intense haemorrhage. Proper treatment needs to differentiate diagnosis with angular pregnancy, which refers to an implantation at least 1 cm from lateral angles of uterine cavity. Ultrasound diagnosis is based
on the following criteria: empty uterine cavity, separate sac at least 1 cm from the lateral edge and a thin (⬍ 5 mm) myometrial layer surrounding the sac. Colour Doppler is used to assess the grade of chorionic villi invasion. There are no data in the literature on the diagnostic value of β-hCG, but we have noticed that IP values
Figure 2. Colour Doppler sonography evidenced rich blood flow at the periphery of the gestational sac with low resistance pattern.
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Figure 3. Value of β-hCG and diameter of gestational sac during the treatment and in the following days in case 1.
are higher than tubal and similar to intrauterine pregnancies, due to higher blood vessel intensity inside the surrounding myometrial mantle. In addition, myometrial mantle-thickness is a key marker for differential diagnosis with angular pregnancy. In fact while in IP there is a paucity of myometrium around the superolateral portion of the sac; angular the thickness will be at least 5 mm (Doubilet and Benson 2003). Ultrasound diagnosis is based mainly on the interstitial line sign, which refers to an echogenic line that runs from the endometrial cavity to the cornual region, abutting the interstitial mass (Ackerman et al. 1993). These findings are accompanied by an intense blood flow showing a ‘ring of fire’ around an ectopic pregnancy and rising levels of β-hCG, much more than those observed in other tubal pregnancies (Dialani and Levine 2004).
The choice of treatment depends mainly on the presence of prompt diagnosis, clinical symptomatology and future fertility. The high proportions of IP which are treated with success, using MTX, are related with the great vascularisation that surrounds the ectopic implant. A single dose of MTX i.m. 50 mg/m2 body surface area is successful in more than 80% of cases, if β-hCG level is ⬍ 5,000 IU/l. Whenever the rate of β-hCG levels do not fall by 15% between days 4 and 7 after the first administration, a 2nd dose may be necessary. Although single dose MTX treatment is associated with low liver and bone morrow toxicity, recent data reported that, in ectopic pregnancy and in particular in IP, this protocol is associated with a more frequent incidence of failure and a longer time to decrease (Dilbaz et al. 2005; Barnhart 2012). Considering the slow declining rate of β-hCG and the high values in two of the three cases, we preferred the multidose regimen, even in the 3rd case, with lower β-hCG levels, single dose treatment could have been administered. We have noticed that multidose regimen induces a plateau or a significant decline of β-hCG levels from the 6th to 8th day onwards, after the 3rd MTX dose, with size and blood supply reduction of the ectopic mass at the 8th MTX day. Colour Doppler blood flow analysis records the changes in vascular intensity of trophoblastic tissue that is strongly associated with decline in serial measurement of β-hCG. The time from treatment to complete resolution ranges from 19–129 days. In our cases, the β-hCG fell gradually to non-pregnant levels within 36 days. Very little data are available on long-term follow-up after medical treatment. Several reports raise the concern of IP recurrence at the same site after medical treatment, due to the persistence of previous pathological conditions. We want to focus attention on the crucial importance of an appropriate follow-up evaluation, performing hysterosalpingography and hysteroscopy confirming the tubal patency on the side of IP, avoiding in this manner, IP recurrences. Furthermore, we recommend hysteroscopy due to its important role in ensuring or maintaining tubal patency, with the aid of tubal spilling after an IP. We underline also the successful role of the MTX multidose regimen in IP cases with higher values of β-hCG, even in cases of embryonic vitality and advanced IP as in our second case. The
Figure 4. Ultrasound monitoring on the 8th day after administration of MTX revealed a gradual reduction in the size of the ectopic mass and a significant reduction in the blood supply.
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Prenatal ultrasound diagnosis of a fetal testis granulosa cell tumour T. Illescas, R. M. Ibba, M. A. Zoppi, A. Iuculano, R. Contu & G. Monni Department of Prenatal Genetic Diagnosis and Fetal Therapy, Ospedale Microcitemico, Cagliari, Italy DOI: 10.3109/01443615.2013.828024 Correspondence: G. Monni, Department of Prenatal Genetic Diagnosis and Fetal Therapy, Ospedale Microcitemico, Via Edward Jenner 09121, Cagliari, Italy. E-mail: [email protected]
Introduction
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Figure 5. Value of β-hCG and diameter of gestational sac during the treatment and in the following days in case 2.
awareness of dangerous complications must be taken into account and physicians should be aware that the presence of a surgeon to expedite non-invasive surgery is essential for fertility outcome. The present report underlines an integrated approach in diagnosis, multidose treatment and close follow-up, which are essential forms of management in this rare occurrence. Furthermore, these pathological conditions require a high index of suspicion, due to frequently misdiagnosis. Hospitalisation is necessary for patients whose condition is unstable, in cases of diagnostic uncertainty and when non-surgical treatment is attempted in case of high values of β-hCG. Finally, the efficacy of medical treatment after a prompt diagnosis, in our experience, is confirmed not only by immediate results in terms of resolution without complication, but also by long-term results confirmed by instrumental procedure, avoiding in this manner the risk of recurrences. Careful antenatal surveillance with a planned caesarean delivery at term should be the safest approach for subsequent pregnancies. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Ackerman TE, Levi CS, Dashefsky SM, Holt SC, Lindsay DJ. 1993. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 189:83–87. Barnhart KT. 2012. Early pregnancy failure: beware of the pitfalls of modern management. Fertility and Sterility 98:1061–1065. Damario MA, Rock JA. 2003. Ectopic pregnancy. In: Rock JA, Jones HW 3rd, editors. Te Linde’s operative gynecology. Philadelphia: Lippincott, Williams & Wilkins. p 507–536. Dialani V, Levine D. 2004. Ectopic pregnancy: a review. Ultrasound Quarterly 20:105–117. Dilbaz S, Katas B, Demir B, Dilbaz B. 2005. Treating cornual pregnancy with a single methotrexate injection: a report of 3 cases. Journal of Reproductive Medicine 50:141–144. Doubilet P, Benson CB. 2003. Atlas of ultrasound in obstetrics and gynecology: a multimedia reference. Philadelphia: Lippincott, Williams & Wilkins. Moawad NS, Mahajan ST, Moniz MH, Taylor SE, Hurd WW. 2010. Current diagnosis and treatment of interstitial pregnancy. American Journal of Obstetrics and Gynecology 202:15–29. Stovall TG, Ling FW. 1993. Single-dose methotrexate: an expanded clinical trial. American Journal of Obstetrics and Gynecology 168:1759–1762. Tulandi T, Al-Jaroudi D. 2004. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry. Obstetrics and Gynecology 103:47–45. Walker JJ. 2007. Ectopic pregnancy. Clinical Obstetrics and Gynecology 50:89–99. Walsen O. 1957. Interstitial pregnancy in the fifth month of pregnancy with fatal rupture of the uterus. Medizinische Klinik (Munich) 52: 2250–2253.
Normally, by the 5th month of pregnancy, the fetal testes lie close to the deep inguinal ring and begin to descend to the scrotum during the 7th month. The testicles should be found in the scrotal sac at 36 weeks’ gestation and it is at this stage, we can search for pathology through the examination of the scrotal sac. Cryptorchidism is a common finding in full-term newborns, with a reported rate of 3.4% (Shih et al. 1997). Scrotal masses detected prenatally are rare entities with the exception of hydrocoele. Tumours are considered congenital when found up to the first 3 months of life, accounting for ⬍ 2% of all paediatric tumours. The most frequent type is extracranial teratoma (mainly sacrococcygeal) (Alamo et al. 2011). We present here a case of a fetal scrotal tumour, diagnosed and followed in Ospedale Microcitemico, Cagliari, Italy.
Case report A healthy 32-year-old woman, gravida 1 para 0, had a normal singleton low-risk pregnancy until the 3rd trimester. At 36 weeks, she was referred to our Centre for evaluation of a non-reassuring image in the fetal left testicle found during a routine fetal growth scan. We confirmed the presence of an increased-sized left testicle (2 ⫻ 2.5 ⫻ 3 cm) with a heterogeneous image, with little sonolucent areas, scarce blood flow with Doppler and no evidence of peristaltic movements inside (Figures 1 and 2). The right testicle was homogeneous and 1.5 ⫻ 1 cm in size. There were no signs of intestinal obstruction or ascites. No other fetal abnormalities were found and the biometry was appropriated for gestational age. The diagnostic possibilities stated were: scrotal tumour (teratoma), inguinoscrotal hernia and testicular torsion. During the next 2 weeks, the mass remained stable in size and blood flow pattern (showing arterial and venous flow). 3D-volumes were acquired and assessed but they did not add any significant information to the diagnosis (Figure 3). The patient had an uneventful vaginal delivery at 38 ⫹ 2 weeks’ gestation. A male weighing 3,710 g was born. The ultrasonographic prenatal finding was then confirmed by magnetic resonance image (MRI, Figure 4) to be a testicular tumour and the baby was referred to the paediatric oncologists. Two months after birth, a radical orchiectomy was performed. Pathological examination showed a juvenile granulosa cell tumour.
Discussion The differential diagnosis of a fetal scrotal mass includes: • Hydrocoele: The most common diagnosis of a fetal scrotal mass and the ultrasound characteristic of this condition is the appearance of an anechoic collection of fluid surrounding an easily recognisable testis (Pretorius et al. 1998). • Inguinoscrotal hernia: Fetal inguinal hernia is rarely diagnosed because the gradient of intra-abdominal pressure usually rises only after birth. The key finding for the diagnosis consists of peristaltic waves and loops of small bowel trapped in the scrotum, with blood flow visible on coloor Doppler imaging of the scrotal mass (Frati et al. 2008). • Testicular torsion: Appears as an enlarged testis with an echogenic rim and heterogeneous parenchyma, surrounded by haemorrhagic
ISSN: 0144-3615 (Print) 1364-6893 (Online) Journal homepage: http://www.tandfonline.com/loi/ijog20
Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of nonruptured interstitial pregnancy A. Pellegrino, G. R. Damiani, S. Landi, M. Tartagni, S. Tafuri, A. Caringella, C. Sportelli, M. Gaetani & G. Loverro To cite this article: A. Pellegrino, G. R. Damiani, S. Landi, M. Tartagni, S. Tafuri, A. Caringella, C. Sportelli, M. Gaetani & G. Loverro (2014) Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of non-ruptured interstitial pregnancy, Journal of Obstetrics and Gynaecology, 34:1, 93-95 To link to this article: http://dx.doi.org/10.3109/01443615.2013.789834
Published online: 20 Dec 2013.
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Article views: 86
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View Crossmark data
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Date: 05 November 2015, At: 18:35
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Obstetric Case Reports 93 Deans R, Abbott J. 2010. Hysteroscopic management of cesarean scar ectopic pregnancy. Fertility and Sterility 93:1735–1740. Jurkovic D, Hillaby K, Woelfer B et al. 2003. First-trimester diagnosis and management of pregnancies implanted into the lower uterine segment Cesarean section scar. Ultrasound in Obstetrics and Gynecology 21:220–227. Maymon R, Halperin R, Mendlovic S et al. 2004. Ectopic pregnancies in Caesarean section scars: the 8 year experience of one medical centre. Human Reproduction 19:278–284. Rotas MA, Haberman S, Levgur M. 2006. Cesarean scar ectopic pregnancies: etiology, diagnosis, and management. Obstetrics and Gynecology 107: 1373–1381. Seow KM, Huang LW, Lin YH et al. 2004. Cesarean scar pregnancy: issues in management. Ultrasound in Obstetrics and Gynecology 23:247–253. Shih JC. 2004. Cesarean scar pregnancy: diagnosis with three-dimensional (3D) ultrasound and 3D power Doppler. Ultrasound in Obstetrics and Gynecology 23:306–307. Tagore S, Teo SH, Chua SY et al. 2010. A retrospective review of uterine scar pregnancies: single centre experience. Archives of Gynecology and Obstetrics 282:711–715. Vial Y, Petignat P, Hohlfeld P. 2000. Pregnancy in a cesarean scar. Ultrasound in Obstetrics and Gynecology 16:592–593. Wang YL, Su TH, Chen HS. 2006. Operative laparoscopy for unruptured ectopic pregnancy in a caesarean scar. British Journal of Obstetrics and Gynaecology 113:1035–1038.
Pivotal points in interstitial pregnancy: New insights in conservative medical treatment of non-ruptured interstitial pregnancy A. Pellegrino1, G. R. Damiani1, S. Landi2, M. Tartagni3, S. Tafuri4, A. Caringella3, C. Sportelli5, M. Gaetani3 & G. Loverro3 Department of Obstetrics and Gynecology, 1Malzoni Hospital, Lecco, 2Sondrio Hospital, Sondrio, 3University of Bari, Policlinico 4Department of Biomedical Sciences, Section of Hygiene, ‘Aldo Moro’ University, Bari and 5Alessandro Manzoni Hospital, Lecco, Italy DOI: 10.3109/01443615.2013.789834 Correspondence: G. R. Damiani, Department of Obstetrics and Gynecology, Malzoni Hospital, Lecco, Italy. E-mail: [email protected]
We report the efficacy of a minimally invasive approach of the multidose protocol with methotrexate (MTX) in the management of three cases of interstitial pregnancy (IP), with elevated serum b-hCG in two cases. New considerations and management strategies are discussed. Successful termination of IP and in one case, a subsequent successful pregnancy, was achieved. The process led to the development of an enhanced understanding of diagnostic modalities and their limitations, with regard to the particular entities under discussion. We also focused attention on pivotal points and anatomical features in the management of this dangerous occurrence. Long-term results with careful follow-up were analysed by instrumental procedure. This hazardous type of ectopic pregnancy can be managed with systemic administration of MTX, also in patients with elevated β-hCG values. The present report underlines that an integrated approach in early diagnosis, multidose treatment and close follow-up, are essential forms of medical management. Keywords: Cornual pregnancy, fallopian tube, interstitial pregnancy, methotrexate, multidose protocol
Introduction Interstitial pregnancy (IP) accounts for 2–4% of tubal pregnancies and is an ectopic pregnancy located outside of the uterine cavity, in the first part of the fallopian tube, surrounded by the muscular layer of the uterus, which allows a significant expansion when it hosts a pregnancy, but delays the clinical symptoms characterised
by heavy haemorrhage and high mortality rate (2.5%) (Damario and Rock 2003; Moawad et al. 2010; Tulandi and Al-Jaroudi 2004; Walsen 1957). Early diagnosis is mandatory in order to avoid massive transfusions and detrimental effects of surgery on future fertility, like cornual wedge resection or total hysterectomy (Walker 2007). The choice of treatment is still under discussion, although preliminary data revealed that medical treatment with methotrexate (MTX) is the gold standard, as in other ectopic pregnancies (Stovall and Ling 1993).
Case report 1 A 39-year-old nulliparous primigravida, presented to our institution with 7 weeks’ amenorrhoea, with recurrent vaginal bleeding lasting for 1 week. The β-hCG value was 8,166 mUI/ml, rising to 8,971 mUI/ml after 48 h. A transvaginal scanning revealed a 23 mm gestational sac at the right superolateral portion of the uterus, corresponding to 5 weeks’ gestational age, with no signs of embryonic viability, surrounded by a thin myometrium (⬍ 5 mm), outside of the empty uterine cavity and the interstitial line sign (Figure 1). These parameters have been interpreted as suggestive of an IP. Colour Doppler evidenced rich blood flow, with an image of a ring of fire, surrounding the sac and spectral tracing revealed a low resistance pattern, characteristic of trophoblastic blood flow (Figure 2). The patient was counselled about the ectopic implantation, the associated risks and all putative treatment regimens. Considering the rising levels of β-hCG and the patient’s desire to preserve fertility, systemic MTX administration was performed, at the dose of 1 mg/kg plus folinic acid 0, 1 mg/kg on days 0,2,4,6. Close follow-up was made, monitoring β-hCG and with ultrasound. The significant decline in the levels of β-hCG was observed from the 6th to 7th day onwards (Figure 3). Ultrasound monitoring revealed a gradual reduction in the size of the ectopic gestation from 24 mm to 16 mm, with a significant synchronous reduction of blood supply on the 8th day of MTX administration (Figure 4). The β-hCG fell gradually to non-pregnant levels within 36 days. After 6 months, hysteroscopy revealed a normal uterine cavity. A normal pregnancy occurred after 8 months, ending with a caesarean section for fetal distress.
Case report 2 A 37-year-old nulliparous woman, with 9 weeks’ amenorrhoea, presented to us complaining of vaginal spotting and acute abdominal pain. A transvaginal scan showed an eccentrically gestational sac of 29 mm, with embryonic viability, located at the outer right angle of fibromatous uterus. The pregnancy appeared implanted on the right extremity, where no myomas were present. The site of the gestational sac and the presence of the interstitial line sign suggested IP. The initial β-hCG value was 24, 213 mIU/l. MTX multidose protocol was administered as described above. On the 4th day, the β-hCG value was 16, 600 mIU/l, at the end of treatment on the 8th day 12, 1,312 mIU/l (Figure 5). Ultrasounds were performed on days 2, 5, 10 and then weekly until the risk of rupture, due to persistent trophoblastic proliferation, was presumed to disappear. This risk was evaluated by Doppler flow persistence in implantation site, which disappeared after 10 days from the beginning of treatment when the β-hCG level was 14.181 mIU/l. Ultrasound confirmed the resolution of the ectopic mass, 15 days after the termination of treatment.
Case report 3 A 33-year-old nulliparous woman with 7 weeks’ amenorrhoea, after a successful cycle of IVF, presented in our institution for vaginal bleeding. Ultrasonography revealed a singleton gestation, eccentrically placed in the left utero-tubal junctional area, lying 1 cm outside the most upper lateral edge of the decidualised cavity, measuring 0.4 cm. No embryo was visualised. Spectral tracing revealed a low resistant pattern deriving from trophoblastic tissue. The initial β-hCG was 1,351 mIU/l. Multidose protocol was administered. On the 8th day, β-hCG was 1,451 mIU/l, after 1 week 115 mIU/l and after another 5 days, the β-hCG level fell to 3 mIU/l.
Discussion The surrounding muscular wall of the interstitial portion confers ability to expand higher than other parts of fallopian tube.
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Figure 1. 3D-transvaginal scan revealed a small gestational sac (GS) at right superolateral portion of the uterus, surrounded by a thin myometrium (⬍ 5 mm), outside of the empty uterine cavity and the interstitial line sign (I.L.).
Therefore, the rupture is more delayed if compared with other portions, although IP is accompanied by a more intense haemorrhage. Proper treatment needs to differentiate diagnosis with angular pregnancy, which refers to an implantation at least 1 cm from lateral angles of uterine cavity. Ultrasound diagnosis is based
on the following criteria: empty uterine cavity, separate sac at least 1 cm from the lateral edge and a thin (⬍ 5 mm) myometrial layer surrounding the sac. Colour Doppler is used to assess the grade of chorionic villi invasion. There are no data in the literature on the diagnostic value of β-hCG, but we have noticed that IP values
Figure 2. Colour Doppler sonography evidenced rich blood flow at the periphery of the gestational sac with low resistance pattern.
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Figure 3. Value of β-hCG and diameter of gestational sac during the treatment and in the following days in case 1.
are higher than tubal and similar to intrauterine pregnancies, due to higher blood vessel intensity inside the surrounding myometrial mantle. In addition, myometrial mantle-thickness is a key marker for differential diagnosis with angular pregnancy. In fact while in IP there is a paucity of myometrium around the superolateral portion of the sac; angular the thickness will be at least 5 mm (Doubilet and Benson 2003). Ultrasound diagnosis is based mainly on the interstitial line sign, which refers to an echogenic line that runs from the endometrial cavity to the cornual region, abutting the interstitial mass (Ackerman et al. 1993). These findings are accompanied by an intense blood flow showing a ‘ring of fire’ around an ectopic pregnancy and rising levels of β-hCG, much more than those observed in other tubal pregnancies (Dialani and Levine 2004).
The choice of treatment depends mainly on the presence of prompt diagnosis, clinical symptomatology and future fertility. The high proportions of IP which are treated with success, using MTX, are related with the great vascularisation that surrounds the ectopic implant. A single dose of MTX i.m. 50 mg/m2 body surface area is successful in more than 80% of cases, if β-hCG level is ⬍ 5,000 IU/l. Whenever the rate of β-hCG levels do not fall by 15% between days 4 and 7 after the first administration, a 2nd dose may be necessary. Although single dose MTX treatment is associated with low liver and bone morrow toxicity, recent data reported that, in ectopic pregnancy and in particular in IP, this protocol is associated with a more frequent incidence of failure and a longer time to decrease (Dilbaz et al. 2005; Barnhart 2012). Considering the slow declining rate of β-hCG and the high values in two of the three cases, we preferred the multidose regimen, even in the 3rd case, with lower β-hCG levels, single dose treatment could have been administered. We have noticed that multidose regimen induces a plateau or a significant decline of β-hCG levels from the 6th to 8th day onwards, after the 3rd MTX dose, with size and blood supply reduction of the ectopic mass at the 8th MTX day. Colour Doppler blood flow analysis records the changes in vascular intensity of trophoblastic tissue that is strongly associated with decline in serial measurement of β-hCG. The time from treatment to complete resolution ranges from 19–129 days. In our cases, the β-hCG fell gradually to non-pregnant levels within 36 days. Very little data are available on long-term follow-up after medical treatment. Several reports raise the concern of IP recurrence at the same site after medical treatment, due to the persistence of previous pathological conditions. We want to focus attention on the crucial importance of an appropriate follow-up evaluation, performing hysterosalpingography and hysteroscopy confirming the tubal patency on the side of IP, avoiding in this manner, IP recurrences. Furthermore, we recommend hysteroscopy due to its important role in ensuring or maintaining tubal patency, with the aid of tubal spilling after an IP. We underline also the successful role of the MTX multidose regimen in IP cases with higher values of β-hCG, even in cases of embryonic vitality and advanced IP as in our second case. The
Figure 4. Ultrasound monitoring on the 8th day after administration of MTX revealed a gradual reduction in the size of the ectopic mass and a significant reduction in the blood supply.
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Obstetric Case Reports
Prenatal ultrasound diagnosis of a fetal testis granulosa cell tumour T. Illescas, R. M. Ibba, M. A. Zoppi, A. Iuculano, R. Contu & G. Monni Department of Prenatal Genetic Diagnosis and Fetal Therapy, Ospedale Microcitemico, Cagliari, Italy DOI: 10.3109/01443615.2013.828024 Correspondence: G. Monni, Department of Prenatal Genetic Diagnosis and Fetal Therapy, Ospedale Microcitemico, Via Edward Jenner 09121, Cagliari, Italy. E-mail: [email protected]
Introduction
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Figure 5. Value of β-hCG and diameter of gestational sac during the treatment and in the following days in case 2.
awareness of dangerous complications must be taken into account and physicians should be aware that the presence of a surgeon to expedite non-invasive surgery is essential for fertility outcome. The present report underlines an integrated approach in diagnosis, multidose treatment and close follow-up, which are essential forms of management in this rare occurrence. Furthermore, these pathological conditions require a high index of suspicion, due to frequently misdiagnosis. Hospitalisation is necessary for patients whose condition is unstable, in cases of diagnostic uncertainty and when non-surgical treatment is attempted in case of high values of β-hCG. Finally, the efficacy of medical treatment after a prompt diagnosis, in our experience, is confirmed not only by immediate results in terms of resolution without complication, but also by long-term results confirmed by instrumental procedure, avoiding in this manner the risk of recurrences. Careful antenatal surveillance with a planned caesarean delivery at term should be the safest approach for subsequent pregnancies. Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.
References Ackerman TE, Levi CS, Dashefsky SM, Holt SC, Lindsay DJ. 1993. Interstitial line: sonographic finding in interstitial (cornual) ectopic pregnancy. Radiology 189:83–87. Barnhart KT. 2012. Early pregnancy failure: beware of the pitfalls of modern management. Fertility and Sterility 98:1061–1065. Damario MA, Rock JA. 2003. Ectopic pregnancy. In: Rock JA, Jones HW 3rd, editors. Te Linde’s operative gynecology. Philadelphia: Lippincott, Williams & Wilkins. p 507–536. Dialani V, Levine D. 2004. Ectopic pregnancy: a review. Ultrasound Quarterly 20:105–117. Dilbaz S, Katas B, Demir B, Dilbaz B. 2005. Treating cornual pregnancy with a single methotrexate injection: a report of 3 cases. Journal of Reproductive Medicine 50:141–144. Doubilet P, Benson CB. 2003. Atlas of ultrasound in obstetrics and gynecology: a multimedia reference. Philadelphia: Lippincott, Williams & Wilkins. Moawad NS, Mahajan ST, Moniz MH, Taylor SE, Hurd WW. 2010. Current diagnosis and treatment of interstitial pregnancy. American Journal of Obstetrics and Gynecology 202:15–29. Stovall TG, Ling FW. 1993. Single-dose methotrexate: an expanded clinical trial. American Journal of Obstetrics and Gynecology 168:1759–1762. Tulandi T, Al-Jaroudi D. 2004. Interstitial pregnancy: results generated from the Society of Reproductive Surgeons Registry. Obstetrics and Gynecology 103:47–45. Walker JJ. 2007. Ectopic pregnancy. Clinical Obstetrics and Gynecology 50:89–99. Walsen O. 1957. Interstitial pregnancy in the fifth month of pregnancy with fatal rupture of the uterus. Medizinische Klinik (Munich) 52: 2250–2253.
Normally, by the 5th month of pregnancy, the fetal testes lie close to the deep inguinal ring and begin to descend to the scrotum during the 7th month. The testicles should be found in the scrotal sac at 36 weeks’ gestation and it is at this stage, we can search for pathology through the examination of the scrotal sac. Cryptorchidism is a common finding in full-term newborns, with a reported rate of 3.4% (Shih et al. 1997). Scrotal masses detected prenatally are rare entities with the exception of hydrocoele. Tumours are considered congenital when found up to the first 3 months of life, accounting for ⬍ 2% of all paediatric tumours. The most frequent type is extracranial teratoma (mainly sacrococcygeal) (Alamo et al. 2011). We present here a case of a fetal scrotal tumour, diagnosed and followed in Ospedale Microcitemico, Cagliari, Italy.
Case report A healthy 32-year-old woman, gravida 1 para 0, had a normal singleton low-risk pregnancy until the 3rd trimester. At 36 weeks, she was referred to our Centre for evaluation of a non-reassuring image in the fetal left testicle found during a routine fetal growth scan. We confirmed the presence of an increased-sized left testicle (2 ⫻ 2.5 ⫻ 3 cm) with a heterogeneous image, with little sonolucent areas, scarce blood flow with Doppler and no evidence of peristaltic movements inside (Figures 1 and 2). The right testicle was homogeneous and 1.5 ⫻ 1 cm in size. There were no signs of intestinal obstruction or ascites. No other fetal abnormalities were found and the biometry was appropriated for gestational age. The diagnostic possibilities stated were: scrotal tumour (teratoma), inguinoscrotal hernia and testicular torsion. During the next 2 weeks, the mass remained stable in size and blood flow pattern (showing arterial and venous flow). 3D-volumes were acquired and assessed but they did not add any significant information to the diagnosis (Figure 3). The patient had an uneventful vaginal delivery at 38 ⫹ 2 weeks’ gestation. A male weighing 3,710 g was born. The ultrasonographic prenatal finding was then confirmed by magnetic resonance image (MRI, Figure 4) to be a testicular tumour and the baby was referred to the paediatric oncologists. Two months after birth, a radical orchiectomy was performed. Pathological examination showed a juvenile granulosa cell tumour.
Discussion The differential diagnosis of a fetal scrotal mass includes: • Hydrocoele: The most common diagnosis of a fetal scrotal mass and the ultrasound characteristic of this condition is the appearance of an anechoic collection of fluid surrounding an easily recognisable testis (Pretorius et al. 1998). • Inguinoscrotal hernia: Fetal inguinal hernia is rarely diagnosed because the gradient of intra-abdominal pressure usually rises only after birth. The key finding for the diagnosis consists of peristaltic waves and loops of small bowel trapped in the scrotum, with blood flow visible on coloor Doppler imaging of the scrotal mass (Frati et al. 2008). • Testicular torsion: Appears as an enlarged testis with an echogenic rim and heterogeneous parenchyma, surrounded by haemorrhagic
