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Unusual case of recurrent heterotopic pregnancy after bilateral salpingectomy and literature review
Reproductive BioMedicine Online (2013) 26, 59– 61
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SHORT COMMUNICATION
Unusual case of recurrent heterotopic pregnancy after bilateral salpingectomy and literature review Tal Shavit *, Einat Paz-Shalom, Eylon Lachman, Ofer Fainaru, Adrian Ellenbogen IVF Unit, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Technion Faculty of Medicine, Hadera, Israel * Corresponding author. E-mail address: [email protected] (T Shavit). Tal Shavit graduated from the Ben Gurion University in 2004 with his MD and in 2005 with his MHH degree. He completed his specialization in obstetrics and gynaecology in 2011. Since then he has worked as an attending physician in the Hillel-Yaffe IVF unit. He is a member of the Israeli Fertility Association. His special research interests are IVF treatment outcomes.
Abstract Heterotopic pregnancy occurs in up to 1% of pregnancies after IVF and embryo transfer. A case of a 35-year-old woman
undergoing IVF treatment who had had previous laparoscopic bilateral salpingectomy due to hydrosalpinges is presented. She had had two heterotopic pregnancies in both tubal stumps in consecutive pregnancies achieved by IVF. The intrauterine pregnancies ended in spontaneous abortions. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in a cycle, especially when an inappropriately high serum b-human chorionic gonadotrophin concentration is associated with an ultrasound finding of singleton intrauterine pregnancy. RBMOnline ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. KEYWORDS: bilateral salpingectomy, heterotopic pregnancy, IVF
Introduction
Case report
Heterotopic pregnancy is defined as simultaneous occurrence of intrauterine and ectopic pregnancy. It occurs in up to 1% of pregnancies following IVF (Dor et al., 1991). A few cases of heterotopic pregnancy after bilateral salpingectomy following IVF have been reported. This article reports a case of recurrent heterotopic pregnancy after IVF in a patient with bilateral salpingectomy prior to her first pregnancy.
A 35-year-old woman was referred to the IVF unit with primary infertility. Physical examination, hormonal profile and sperm analysis were normal. Hysterosalpingography performed elsewhere demonstrated a normal uterine cavity with bilateral sactosalpinges, confirmed by transvaginal ultrasound. Two IVF cycles were unsuccessful. Before the third IVF trial, operative laparoscopic bilateral salpingectomy
1472-6483/$ - see front matter ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.rbmo.2012.10.006
60 was performed. Stumps of less than 3 mm were coagulated. A third IVF cycle was performed. Six oocytes were retrieved and all were fertilized. Under ultrasound guidance, two embryos in 40 l medium were transferred on day 3 with a soft catheter 0.5–1 cm from the uterine fundus. Pregnancy was confirmed 12 days later, serum b-human chorionic gonadotrophin (HCG) concentration being 300 IU/ml and 2 days later 655 mIU/ml. After 2 weeks, transvaginal ultrasound examination showed an intrauterine viable pregnancy with an additional gestational sac in the right tubal stump and a large amount of fluid in the Douglas pouch. On laparoscopy, hem peritoneum and ruptured right tube were diagnosed. The stump was resected and coagulated. Examination of the left uterine cornua demonstrated a short left tubal stump. Before discharge, ultrasound examination revealed a 6-week intrauterine pregnancy with fetal cardiac activity. Missed abortion was diagnosed 2 weeks later and uterine evacuation was performed. In the fourth IVF cycle, two embryos were transferred as described above. Serum b-HCG concentration 12 days after embryo transfer was 109 IU/ml and 266 IU/ml 2 days later. Transvaginal ultrasound examination 2 weeks later revealed a heterotopic pregnancy – an intrauterine embryo with fetal cardiac activity and a second gestational sac in the left tubal stump. Operative laparoscopy was undertaken and the stump was removed. Spontaneous abortion of the intrauterine pregnancy occurred several days later. Before commencing another IVF cycle, the patient underwent diagnostic hysteroscopy. An uterine septum of 30% of the uterine length was noted and excised. In the fifth and sixth cycles, two embryos were replaced as described above. Pregnancy was not achieved. An intrauterine pregnancy was achieved in the seventh IVF cycle. At 19 weeks of gestation, 2 weeks after amniocentesis, ultrasound examination diagnosed a late missed abortion. Termination of pregnancy was achieved by extraamniotic prostaglandin E2 administration followed by curettage. In the eighth IVF cycle, intrauterine pregnancy was achieved. At 34 weeks of gestation, Caesarean section was performed due to premature rupture of membranes and a transverse lie. A healthy male fetus weighing 2450 g was born.
Discussion The frequency of heterotopic pregnancy, although still uncommon, has increased during the assisted reproduction era. Updated studies show an incidence of 1 in 100 assisted reproduction pregnancies (Dor et al., 1991). Salpingectomy for hydrosalpinges has lately become an accepted method for improving outcomes in a selected group of patients undergoing IVF for tubal disease (Johnson et al., 2010). Such procedures do not include excision of the patent cornual and intramural segment of the damaged tube. It is suggested that tubes should be removed, with attention paid to salpingectomy or tubal clipping, as close to the cornual aspect of the uterus as possible to eliminate the risk of ectopic pregnancy. Abdominal pain and vaginal bleeding are common symptoms that raise the suspicion of ectopic pregnancy, especially in assisted reproduction pregnancies. Unfortunately,
T Shavit et al. in the presence of an intrauterine pregnancy, the dictum ‘think ectopic’ is sometimes forgotten. Thus, thorough ultrasound examination in these patients is important. Talbot et al. (2011) found that 71% of women with heterotopic pregnancy had at least one risk factor for ectopic pregnancy: assisted reproduction treatment, known damage to the Fallopian tubes, previous pelvic inflammatory disease, previous ectopic pregnancy, periadnexal adhesions and endometriosis. The incidence of recurrent heterotopic pregnancy is low. Assuming each pregnancy is independent, and since the incidence of heterotopic pregnancy following IVF is 1:100, the incidence of recurrent heterotopic pregnancy would be 1:10,000 and after bilateral salpingectomy the incidence could be even lower. Heterotopic pregnancy can be treated by surgery, medical treatment or expectancy, although the main aim is to be minimally invasive in order to preserve the intrauterine pregnancy. Methotrexate is usually avoided so as to not compromise the viable intrauterine pregnancy. The use of potassium chloride or hyperosmolar injection directly on the ectopic pregnancy had been reported. Barrenetxea et al. (2007) found that 78% of the patients with heterotopic pregnancies underwent surgery. The survival rate of intrauterine gestations in heterotopic pregnancies is estimated to be 66–68%. Clayton et al. (2007) compared the outcomes of heterotopic and intrauterine pregnancies after assisted reproduction treatment. They found in heterotopic pregnancy that the intrauterine gestations were twice as likely to end in spontaneous abortion and 10 times as likely to end in induced abortion. Moreover, heterotopic intrauterine gestations were 30% less likely to result in live birth than intrauterine pregnancies. Among pregnancies that resulted in live birth, there were no differences in outcomes. In the current report, the two intrauterine heterotopic pregnancies ended in missed abortion after surgical treatment for the ectopic pregnancies. There are several case reports describing heterotopic pregnancies after bilateral salpingectomy in IVF patients (Barrenetxea et al., 2007). As far as is known, this is the first case report regarding recurrent heterotopic pregnancy in an IVF patient who had previously undergone bilateral salpingectomy. This rare case makes it clear that abdominal pain or vaginal bleeding in early pregnancy, despite the presence of an intrauterine pregnancy, should raise the suspicion of heterotopic pregnancy. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in an IVF cycle, especially when an inappropriately high serum b-HCG concentration (>300 IU/l on day 15 after oocyte fertilization) is associated with an ultrasound finding of a singleton intrauterine pregnancy. A single-embryo transfer may be considered in young patients with a history of previous heterotopic pregnancy, which will reduce the risk of recurrence of this pathology.
References Barrenetxea, G., Barinaga-Rementeria, L., Lopez de Larruzea, A., Agirregoikoa, J.A., Mandiola, M., Carbonero, K., 2007. Heterotopic pregnancy: two cases and a comparative review. Fertil. Steril. 87, 417e9–417e15.
Recurrent heterotopic pregnancy after salpingectomy Clayton, H., Schieve, L., Peterson, H., Jameison, D., Reynolds, M., Wright, V., 2007. A comparison of heterotopic and intrauterine only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002. Fertil. Steril. 87, 303–309. Dor, J., Seidman, D.S., Levran, D., Ben-Refael, Z., Ben-Shlomo, I., Mashiach, S., 1991. The incidence of combined intrauterine and extra uterine pregnancy after in-vivo fertilization and embryo transfer. Fertil. Steril. 55, 833–834. Johnson, N., van Voorst, S., Sowter, M.C., Strandell, A., Mol, B.W., 2010. Surgical treatment for tubal disease in women due to
61 undergo in vitro fertilisation. Cochrane Database Syst. Rev. 20 (1), CD002125. Talbot, K., Simpson, R., Price, N., Jackson, S.R., 2011. Heterotopic pregnancy. J. Obstet. Gynecol. 31, 7–12. Declaration: The authors report no financial or commercial conflicts of interest. Received 2 July 2012; refereed 2 September 2012; accepted 4 October 2012.
www.sciencedirect.com www.rbmonline.com
SHORT COMMUNICATION
Unusual case of recurrent heterotopic pregnancy after bilateral salpingectomy and literature review Tal Shavit *, Einat Paz-Shalom, Eylon Lachman, Ofer Fainaru, Adrian Ellenbogen IVF Unit, Department of Obstetrics and Gynecology, Hillel Yaffe Medical Center, Technion Faculty of Medicine, Hadera, Israel * Corresponding author. E-mail address: [email protected] (T Shavit). Tal Shavit graduated from the Ben Gurion University in 2004 with his MD and in 2005 with his MHH degree. He completed his specialization in obstetrics and gynaecology in 2011. Since then he has worked as an attending physician in the Hillel-Yaffe IVF unit. He is a member of the Israeli Fertility Association. His special research interests are IVF treatment outcomes.
Abstract Heterotopic pregnancy occurs in up to 1% of pregnancies after IVF and embryo transfer. A case of a 35-year-old woman
undergoing IVF treatment who had had previous laparoscopic bilateral salpingectomy due to hydrosalpinges is presented. She had had two heterotopic pregnancies in both tubal stumps in consecutive pregnancies achieved by IVF. The intrauterine pregnancies ended in spontaneous abortions. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in a cycle, especially when an inappropriately high serum b-human chorionic gonadotrophin concentration is associated with an ultrasound finding of singleton intrauterine pregnancy. RBMOnline ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. KEYWORDS: bilateral salpingectomy, heterotopic pregnancy, IVF
Introduction
Case report
Heterotopic pregnancy is defined as simultaneous occurrence of intrauterine and ectopic pregnancy. It occurs in up to 1% of pregnancies following IVF (Dor et al., 1991). A few cases of heterotopic pregnancy after bilateral salpingectomy following IVF have been reported. This article reports a case of recurrent heterotopic pregnancy after IVF in a patient with bilateral salpingectomy prior to her first pregnancy.
A 35-year-old woman was referred to the IVF unit with primary infertility. Physical examination, hormonal profile and sperm analysis were normal. Hysterosalpingography performed elsewhere demonstrated a normal uterine cavity with bilateral sactosalpinges, confirmed by transvaginal ultrasound. Two IVF cycles were unsuccessful. Before the third IVF trial, operative laparoscopic bilateral salpingectomy
1472-6483/$ - see front matter ª 2012, Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.rbmo.2012.10.006
60 was performed. Stumps of less than 3 mm were coagulated. A third IVF cycle was performed. Six oocytes were retrieved and all were fertilized. Under ultrasound guidance, two embryos in 40 l medium were transferred on day 3 with a soft catheter 0.5–1 cm from the uterine fundus. Pregnancy was confirmed 12 days later, serum b-human chorionic gonadotrophin (HCG) concentration being 300 IU/ml and 2 days later 655 mIU/ml. After 2 weeks, transvaginal ultrasound examination showed an intrauterine viable pregnancy with an additional gestational sac in the right tubal stump and a large amount of fluid in the Douglas pouch. On laparoscopy, hem peritoneum and ruptured right tube were diagnosed. The stump was resected and coagulated. Examination of the left uterine cornua demonstrated a short left tubal stump. Before discharge, ultrasound examination revealed a 6-week intrauterine pregnancy with fetal cardiac activity. Missed abortion was diagnosed 2 weeks later and uterine evacuation was performed. In the fourth IVF cycle, two embryos were transferred as described above. Serum b-HCG concentration 12 days after embryo transfer was 109 IU/ml and 266 IU/ml 2 days later. Transvaginal ultrasound examination 2 weeks later revealed a heterotopic pregnancy – an intrauterine embryo with fetal cardiac activity and a second gestational sac in the left tubal stump. Operative laparoscopy was undertaken and the stump was removed. Spontaneous abortion of the intrauterine pregnancy occurred several days later. Before commencing another IVF cycle, the patient underwent diagnostic hysteroscopy. An uterine septum of 30% of the uterine length was noted and excised. In the fifth and sixth cycles, two embryos were replaced as described above. Pregnancy was not achieved. An intrauterine pregnancy was achieved in the seventh IVF cycle. At 19 weeks of gestation, 2 weeks after amniocentesis, ultrasound examination diagnosed a late missed abortion. Termination of pregnancy was achieved by extraamniotic prostaglandin E2 administration followed by curettage. In the eighth IVF cycle, intrauterine pregnancy was achieved. At 34 weeks of gestation, Caesarean section was performed due to premature rupture of membranes and a transverse lie. A healthy male fetus weighing 2450 g was born.
Discussion The frequency of heterotopic pregnancy, although still uncommon, has increased during the assisted reproduction era. Updated studies show an incidence of 1 in 100 assisted reproduction pregnancies (Dor et al., 1991). Salpingectomy for hydrosalpinges has lately become an accepted method for improving outcomes in a selected group of patients undergoing IVF for tubal disease (Johnson et al., 2010). Such procedures do not include excision of the patent cornual and intramural segment of the damaged tube. It is suggested that tubes should be removed, with attention paid to salpingectomy or tubal clipping, as close to the cornual aspect of the uterus as possible to eliminate the risk of ectopic pregnancy. Abdominal pain and vaginal bleeding are common symptoms that raise the suspicion of ectopic pregnancy, especially in assisted reproduction pregnancies. Unfortunately,
T Shavit et al. in the presence of an intrauterine pregnancy, the dictum ‘think ectopic’ is sometimes forgotten. Thus, thorough ultrasound examination in these patients is important. Talbot et al. (2011) found that 71% of women with heterotopic pregnancy had at least one risk factor for ectopic pregnancy: assisted reproduction treatment, known damage to the Fallopian tubes, previous pelvic inflammatory disease, previous ectopic pregnancy, periadnexal adhesions and endometriosis. The incidence of recurrent heterotopic pregnancy is low. Assuming each pregnancy is independent, and since the incidence of heterotopic pregnancy following IVF is 1:100, the incidence of recurrent heterotopic pregnancy would be 1:10,000 and after bilateral salpingectomy the incidence could be even lower. Heterotopic pregnancy can be treated by surgery, medical treatment or expectancy, although the main aim is to be minimally invasive in order to preserve the intrauterine pregnancy. Methotrexate is usually avoided so as to not compromise the viable intrauterine pregnancy. The use of potassium chloride or hyperosmolar injection directly on the ectopic pregnancy had been reported. Barrenetxea et al. (2007) found that 78% of the patients with heterotopic pregnancies underwent surgery. The survival rate of intrauterine gestations in heterotopic pregnancies is estimated to be 66–68%. Clayton et al. (2007) compared the outcomes of heterotopic and intrauterine pregnancies after assisted reproduction treatment. They found in heterotopic pregnancy that the intrauterine gestations were twice as likely to end in spontaneous abortion and 10 times as likely to end in induced abortion. Moreover, heterotopic intrauterine gestations were 30% less likely to result in live birth than intrauterine pregnancies. Among pregnancies that resulted in live birth, there were no differences in outcomes. In the current report, the two intrauterine heterotopic pregnancies ended in missed abortion after surgical treatment for the ectopic pregnancies. There are several case reports describing heterotopic pregnancies after bilateral salpingectomy in IVF patients (Barrenetxea et al., 2007). As far as is known, this is the first case report regarding recurrent heterotopic pregnancy in an IVF patient who had previously undergone bilateral salpingectomy. This rare case makes it clear that abdominal pain or vaginal bleeding in early pregnancy, despite the presence of an intrauterine pregnancy, should raise the suspicion of heterotopic pregnancy. The possibility of a heterotopic pregnancy needs to be considered when more than one embryo has been transferred in an IVF cycle, especially when an inappropriately high serum b-HCG concentration (>300 IU/l on day 15 after oocyte fertilization) is associated with an ultrasound finding of a singleton intrauterine pregnancy. A single-embryo transfer may be considered in young patients with a history of previous heterotopic pregnancy, which will reduce the risk of recurrence of this pathology.
References Barrenetxea, G., Barinaga-Rementeria, L., Lopez de Larruzea, A., Agirregoikoa, J.A., Mandiola, M., Carbonero, K., 2007. Heterotopic pregnancy: two cases and a comparative review. Fertil. Steril. 87, 417e9–417e15.
Recurrent heterotopic pregnancy after salpingectomy Clayton, H., Schieve, L., Peterson, H., Jameison, D., Reynolds, M., Wright, V., 2007. A comparison of heterotopic and intrauterine only pregnancy outcomes after assisted reproductive technologies in the United States from 1999 to 2002. Fertil. Steril. 87, 303–309. Dor, J., Seidman, D.S., Levran, D., Ben-Refael, Z., Ben-Shlomo, I., Mashiach, S., 1991. The incidence of combined intrauterine and extra uterine pregnancy after in-vivo fertilization and embryo transfer. Fertil. Steril. 55, 833–834. Johnson, N., van Voorst, S., Sowter, M.C., Strandell, A., Mol, B.W., 2010. Surgical treatment for tubal disease in women due to
61 undergo in vitro fertilisation. Cochrane Database Syst. Rev. 20 (1), CD002125. Talbot, K., Simpson, R., Price, N., Jackson, S.R., 2011. Heterotopic pregnancy. J. Obstet. Gynecol. 31, 7–12. Declaration: The authors report no financial or commercial conflicts of interest. Received 2 July 2012; refereed 2 September 2012; accepted 4 October 2012.