European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 172–176
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Outcome, complications and future fertility in women treated with uterine artery embolization and methotrexate for non-tubal ectopic pregnancy Haim Krissi 1,a,b,*, Liran Hiersch 1,b, Natan Stolovitch a,b, Shmuel Nitke a,b, Arnon Wiznitzer a,b, Yoav Peled a,b a b
The Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
A R T I C L E I N F O
A B S T R A C T
Article history: Received 18 May 2014 Received in revised form 3 September 2014 Accepted 9 September 2014
Objective: To determine the effectiveness and safety of uterine artery methotrexate (MTX) infusion and embolization combined with systemic MTX for treatment of non-tubal ectopic pregnancy. Study design: We retrospectively reviewed the electronic files of all women admitted to a single tertiary, university-affiliated medical center with a diagnosis of non-tubal (cervical, interstitial or cesarean section scar) ectopic pregnancy, who were treated by a combination of uterine artery MTX infusion and embolization and systemic MTX between January 2001 and March 2014. The treatment protocol included a total of 4 MTX injections in doses of 1 mg/kg/day every other day (days 1, 3, 5, 7 of the protocol) alternating with folinic acid 0.1 mg/kg (days 2, 4, 6, 8). The first or second MTX dose was administered by transcatheter intra-arterial injection during the embolization procedure just before injecting Gelfoam for bilateral uterine artery occlusion, and the remaining doses were given intramuscularly. Results: During the study period, 25 women underwent uterine artery infusion and embolization combined with systemic MTX treatment for non-tubal ectopic pregnancy. Ten of the pregnancies were cervical, 9 were interstitial, and 6 were cesarean scar pregnancies. Mean gestational age and beta-human chorionic gonadotropin (b-HCG) level at admission were 68.6 12.9 days and 14,179 (range 436– 61596) IU/L, respectively. Treatment was successful in 24 patients (96%) with mean b-HCG resolution time of 52.6 (6–147) days. Mild immediate side effects were reported including 8 cases (32%) of abdominal discomfort, 3 cases (12%) of groin or leg pain and 3 cases (12%) of puncture-site local skin infection. No serious immediate side effects such as internal vascular bleeding, sepsis or early liver or renal failure were observed. Among 12 women who stated that they tried to conceive and were more than a year from the treatment, 10 (83.3%) had subsequent pregnancy. Conclusion: A combination of uterine artery MTX infusion and embolization with systemic MTX seems to be an effective and safe treatment for non-tubal ectopic pregnancies in women who try to conceive. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Interstitial pregnancy Cervical pregnancy Cesarean scar pregnancy Methotrexate Uterine artery embolization
Introduction Cervical, cesarean section (CS) scar, and interstitial pregnancies are relatively rare forms of ectopic pregnancy accounting for approximately 4% of all ectopic pregnancies [1]. They often lead to
* Corresponding author at: The Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel. Tel.: +972 522528054; fax: +972 39377585. E-mail address: [email protected] (H. Krissi). 1 The first two authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.ejogrb.2014.09.026 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
delay in diagnosis and subsequent morbidity. As most women may wish to conceive again, the surgical approach, which was once considered the only modality, is now reserved for cases of uncontrolled bleeding [2]. A range of conservative treatment options have been suggested and can be categorized as: reduction of blood supply, systemic chemotherapy, and local chemotherapy or feticide [2]. There is no consensus, however, regarding the optimal treatment for women who wish to avoid the surgical procedure. Conservative treatment with systemic methotrexate (MTX) alone has shown favorable
H. Krissi et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 172–176
results in non-tubal ectopic pregnancies, although the effectiveness of this treatment decreased dramatically in high (>10,000 IU/L) levels of beta-human chorionic gonadotropin (b-HCG) or in cases with fetal cardiac activity [3–5]. Uterine artery embolization (UAE) is currently used in obstetrics and gynecology as a treatment modality for uterine fibroids or to control obstetric hemorrhage. Recently, this modality was considered when treating non-tubal ectopic pregnancies [6– 8]. Previous reports, however, had a relatively small sample size [9], or used it in combination with other surgical procedures (e.g. dilation and curettage) to control bleeding and in many cases, an emergency surgical procedure and even hysterectomy were unavoidable [8–10]. Since monotherapy with either systemic MTX or UAE has shown only moderate success rates, we aimed to explore the effectiveness and safety of uterine artery MTX infusion and embolization combined with systemic MTX for treatment of nontubal ectopic pregnancy in women who wish fertility preservation and desire to avoid surgical treatment.
173
pregnancy rupture; (2) have no contraindications for MTX administration; and (3) have no contraindications to UAE, including renal failure, active pelvic infection, clotting disorders, or known allergy to the contrast material. Treatment protocol
Cervical ectopic pregnancies were diagnosed by transvaginal ultrasound, with the features described by Timor-Tritsch et al. [11]: (1) diffuse, amorphous intrauterine echoes; (2) uterine enlargement; (3) absence of intrauterine pregnancy; and (4) enlargement of the cervix. Interstitial pregnancies were diagnosed by the criteria described by Timor-Tritsch et al. [12], which include: (1) an empty uterine cavity; (2) a separate chorionic sac and at least 1 cm from the lateral edge of the uterine cavity, and (3) a thin (
Contents lists available at ScienceDirect
European Journal of Obstetrics & Gynecology and Reproductive Biology journal homepage: www.elsevier.com/locate/ejogrb
Outcome, complications and future fertility in women treated with uterine artery embolization and methotrexate for non-tubal ectopic pregnancy Haim Krissi 1,a,b,*, Liran Hiersch 1,b, Natan Stolovitch a,b, Shmuel Nitke a,b, Arnon Wiznitzer a,b, Yoav Peled a,b a b
The Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel
A R T I C L E I N F O
A B S T R A C T
Article history: Received 18 May 2014 Received in revised form 3 September 2014 Accepted 9 September 2014
Objective: To determine the effectiveness and safety of uterine artery methotrexate (MTX) infusion and embolization combined with systemic MTX for treatment of non-tubal ectopic pregnancy. Study design: We retrospectively reviewed the electronic files of all women admitted to a single tertiary, university-affiliated medical center with a diagnosis of non-tubal (cervical, interstitial or cesarean section scar) ectopic pregnancy, who were treated by a combination of uterine artery MTX infusion and embolization and systemic MTX between January 2001 and March 2014. The treatment protocol included a total of 4 MTX injections in doses of 1 mg/kg/day every other day (days 1, 3, 5, 7 of the protocol) alternating with folinic acid 0.1 mg/kg (days 2, 4, 6, 8). The first or second MTX dose was administered by transcatheter intra-arterial injection during the embolization procedure just before injecting Gelfoam for bilateral uterine artery occlusion, and the remaining doses were given intramuscularly. Results: During the study period, 25 women underwent uterine artery infusion and embolization combined with systemic MTX treatment for non-tubal ectopic pregnancy. Ten of the pregnancies were cervical, 9 were interstitial, and 6 were cesarean scar pregnancies. Mean gestational age and beta-human chorionic gonadotropin (b-HCG) level at admission were 68.6 12.9 days and 14,179 (range 436– 61596) IU/L, respectively. Treatment was successful in 24 patients (96%) with mean b-HCG resolution time of 52.6 (6–147) days. Mild immediate side effects were reported including 8 cases (32%) of abdominal discomfort, 3 cases (12%) of groin or leg pain and 3 cases (12%) of puncture-site local skin infection. No serious immediate side effects such as internal vascular bleeding, sepsis or early liver or renal failure were observed. Among 12 women who stated that they tried to conceive and were more than a year from the treatment, 10 (83.3%) had subsequent pregnancy. Conclusion: A combination of uterine artery MTX infusion and embolization with systemic MTX seems to be an effective and safe treatment for non-tubal ectopic pregnancies in women who try to conceive. ß 2014 Elsevier Ireland Ltd. All rights reserved.
Keywords: Interstitial pregnancy Cervical pregnancy Cesarean scar pregnancy Methotrexate Uterine artery embolization
Introduction Cervical, cesarean section (CS) scar, and interstitial pregnancies are relatively rare forms of ectopic pregnancy accounting for approximately 4% of all ectopic pregnancies [1]. They often lead to
* Corresponding author at: The Helen Schneider Hospital for Women, Rabin Medical Center, Petach Tikva, Israel. Tel.: +972 522528054; fax: +972 39377585. E-mail address: [email protected] (H. Krissi). 1 The first two authors contributed equally to the manuscript. http://dx.doi.org/10.1016/j.ejogrb.2014.09.026 0301-2115/ß 2014 Elsevier Ireland Ltd. All rights reserved.
delay in diagnosis and subsequent morbidity. As most women may wish to conceive again, the surgical approach, which was once considered the only modality, is now reserved for cases of uncontrolled bleeding [2]. A range of conservative treatment options have been suggested and can be categorized as: reduction of blood supply, systemic chemotherapy, and local chemotherapy or feticide [2]. There is no consensus, however, regarding the optimal treatment for women who wish to avoid the surgical procedure. Conservative treatment with systemic methotrexate (MTX) alone has shown favorable
H. Krissi et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 182 (2014) 172–176
results in non-tubal ectopic pregnancies, although the effectiveness of this treatment decreased dramatically in high (>10,000 IU/L) levels of beta-human chorionic gonadotropin (b-HCG) or in cases with fetal cardiac activity [3–5]. Uterine artery embolization (UAE) is currently used in obstetrics and gynecology as a treatment modality for uterine fibroids or to control obstetric hemorrhage. Recently, this modality was considered when treating non-tubal ectopic pregnancies [6– 8]. Previous reports, however, had a relatively small sample size [9], or used it in combination with other surgical procedures (e.g. dilation and curettage) to control bleeding and in many cases, an emergency surgical procedure and even hysterectomy were unavoidable [8–10]. Since monotherapy with either systemic MTX or UAE has shown only moderate success rates, we aimed to explore the effectiveness and safety of uterine artery MTX infusion and embolization combined with systemic MTX for treatment of nontubal ectopic pregnancy in women who wish fertility preservation and desire to avoid surgical treatment.
173
pregnancy rupture; (2) have no contraindications for MTX administration; and (3) have no contraindications to UAE, including renal failure, active pelvic infection, clotting disorders, or known allergy to the contrast material. Treatment protocol
Cervical ectopic pregnancies were diagnosed by transvaginal ultrasound, with the features described by Timor-Tritsch et al. [11]: (1) diffuse, amorphous intrauterine echoes; (2) uterine enlargement; (3) absence of intrauterine pregnancy; and (4) enlargement of the cervix. Interstitial pregnancies were diagnosed by the criteria described by Timor-Tritsch et al. [12], which include: (1) an empty uterine cavity; (2) a separate chorionic sac and at least 1 cm from the lateral edge of the uterine cavity, and (3) a thin (
