- Email: [email protected]
Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection treated by conservative medical treatment
European Journal of Obstetrics & Gynecology and Reproductive Biology 94 (2001) 155–157
www.elsevier.com / locate / ejogrb
Case report
Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection treated by conservative medical treatment Interest of sonographic follow-up Pascal Mock*, Franc¸ois Olivennes, Severin Doumerc, Rene´ Frydman, Herve´ Fernandez ˆ ´ ` , Clamart, France Antoine Beclere Department of Obstetrics and Gynaecology and Reproductive Endocrinology, Hopital Received 30 November 1999; accepted 23 February 2000
Abstract We describe a case of early bilateral tubal pregnancy diagnosed by transvaginal ultrasonography after intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). A follow-up by transvaginal sonography was done with a systematic second scan (5 days) after the first diagnosis of left tubal ectopic pregnancy in case of assisted conception procedure. This follow-up sonographic strategy permitted us to perform a conservative treatment for this case of spontaneous bilateral tubal pregnancy by two consecutive (left then right) in-situ methotrexate injections under vaginal ultrasonographic guidance without any complications. 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ectopic pregnancy; ICSI; Sonography
1. Introduction The incidence of ectopic pregnancy has tripled in the Western World over the past two decades, with a plateauing for the last 10 years as recently shown in the USA [1,2]. In France, it has been estimated to 2% of births [3] and unusual forms of ectopic pregnancy such as simultaneous bilateral tubal implantation are becoming more frequent in particular after in vitro fertilization and embryo transfer (IVF–ET) [4,5]. The diagnosis of bilateral ectopic pregnancy after IVF– ET is difficult and usually performed belatedly by laparoscopy or laparotomy when haemorrhagic complication appears [6,7]. Recently, it was described after IVF–ET and intracytoplasmic sperm injection with a complicated clini-
cal presentation (unilateral tubal rupture) requiring radical surgical procedure by laparoscopy [8]. We describe a case of early bilateral tubal pregnancy diagnosed by transvaginal ultrasonography after ICSI / ET. We were able to perform a medical treatment by two consecutive in-situ methotrexate injections under vaginal ultrasonographic guidance because of an uncomplicated clinical presentation. The present report demonstrates that an early diagnosis of simultaneous bilateral tubal pregnancy is possible when a follow-up by transvaginal sonography with a systematic second scan is proposed systematically in case of assisted conception procedure.
2. Case report ´ ´ et d’Endocrinologie *Corresponding author. Clinique de Sterilite ´ ` 14, Switzerland. Tel.: 141-22-382Gynecologique, HUG, 1211 Geneve 4331; fax: 141-22-382-4310. E-mail address: [email protected] (P. Mock).
A 33-year-old woman with a history of two implantation failures after intracytoplasmic sperm injection (ICSI) for oligo-astheno-teratospermia was enrolled in a third attempt with assisted hatching. A laparoscopy performed less than
0301-2115 / 01 / $ – see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0301-2115( 00 )00315-8
156
P. Mock et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 94 (2001) 155 – 157
6 months before was normal. We proceeded to a new cycle of controlled ovarian stimulation with a single injection of a time-release GnRH (Decapeptyl; Ipsen, Paris, France) 3 mg i.m. (administered on day 2 of the menstrual cycle) followed by administration of human menopausal gonadotropin (Humegon; Organon, Saint-Denis, France). Triggering of ovulation was obtained with hCG (Gonadotrophine Chorionic ‘Endo’, Organon, 10,000 IU, i.m.) administered on criteria of follicular maturation determined by ultrasound and estradiol (E2) findings. Four embryos were transferred transcervically using Frydman’s catheter on day 3. Luteal phase was supported with 300 mg of micronized progesterone (Utrogestan, Besins-Iscovesco Pharmaceuticals, Paris, France) administered daily (100 mg in the morning, 200 mg in the evening) by vaginal route starting on the evening of the ET day. Thirty days later the first transvaginal sonography was performed with a hCG serum level at 1321 mIU / ml. At this time, an asymptomatic left ectopic pregnancy was detected with sonographic pictures of mixed echoid pattern at the left adnexial region measuring 34 mm without intra-abdominal fluid collection. This case allowed us to propose a conservative medical treatment since a low score was calculated (511) according to previously defined criteria [9]. We therefore proceeded to an ultrasound-guided in-situ injection of methotrexate (MTX) (1 mg / kg) using a 22gauge needle. Five days later, a new control by transvaginal scan was required as usual for a pregnancy obtained by IVF / ET. We diagnosed a new tubal pregnancy on the other right side with an endovaginal ultrasound examination showing a latero-uterine mass of 19315 mm (serum hCG51537 mIU / ml and 1724 mIU / ml 3 days before). Similarly, because of a low score (10) we performed a new in situ MTX injection (1 mg / kg) under sonographic guidance. The postoperative period remained uneventful with hCG levels returned to below 10 mIU / ml 34 days after the first injection.
3. Discussion This case illustrates that an early diagnosis of bilateral tubal pregnancy is possible by using a transvaginal ultrasonography follow-up strategy. Indeed, in the present case report, a second scan 5 days after the initial EP diagnosis on the right side showed a contralateral tubal pregnancy before any complication. As mentioned recently, its diagnosis may be difficult because of a delayed controlateral tubal pregnancy with an overlook during the first laparoscopy [10]. It is interesting to note that similarly the diagnosis by scan was made in two steps with a delay of 5 days as if the natural history of both pregnancies was different. Whereas it is well accepted that transvaginal sonography changed the diagnostic algorithm of ectopic pregnancy with an earlier diagnosis [11], its use for the follow-up of
medically treated EP such as local or intramuscular MTX injection is of no benefit in the management of these patients, because the ectopic mass usually increased in size with an amount of fluid in the Douglas cul-de-sac increasing [12]. Therefore, ultrasound is performed only in cases of abnormal clinical signs (pelvic pain) or hCG clearance alterations with increasing or plateauing levels. However, a careful inspection of the controlateral tube may be a very interesting indication compared to other tools such as laparoscopy to avoid complications such as secondary tubal rupture. Furthermore, an early diagnosis of bilateral ectopic pregnancy after embryo transfer may improve the opportunity to perform a medical treatment because of uncomplicated clinical presentation. Indeed, several authors demonstrated that conservative treatment such as intramuscular MTX injection permits a similar fertility rate compared to surgical treatment [13]. Our policy of EP treatment is to perform a conservative treatment with in-situ MTX treatment when it is possible because we are convinced that such a treatment is economically more interesting with a lower cost and a similar rate of fertility. Such a policy, in our view, should similarly be applied to EP after assisted reproductive technology such as IVF. Moreover, routine use of transvaginal sonography for the follow-up of EP following IVF or ICSI may prevent delay in such a threatened diagnosis, less by evaluating the evolution of tubal lesion than through carefully examining and ruling out controlateral tubal pregnancy or intrauterine pregnancy (heterotopic pregnancy) [9]. When ectopic pregnancy is medically or surgically treated, we propose to perform, with a delay of less than 1 week, a systematic second sonography as proposed after IUP to exclude heterotopic pregnancy. Indeed, most often, the controlateral EP is asymptomatic or difficult to differentiate from the pelvic pain secondary to controlled ovarian hyperstimulation or to the medical treatment. In conclusion, the purpose of this case report is not to describe the first medical treatment of bilateral ectopic pregnancy, but to demonstrate the importance in assisted medical procedures to perform routinely a second sonographic control after the first pregnancy localisation, either intrauterine or ectopic.
References [1] Nederlof KP, Lawson HW, Saftlas AF, Atrash HK, Finch EL. Ectopic pregnancy surveillance, United States, 1970–1987. MMWR 1990;39:9. [2] Centers for Disease Control. Ectopic pregnancy, United States, 1988–1989. MMWR 1992;41:591. [3] Job-Spira N, Bouyer J, Pouly JL, Germain E, Coste J, AubletCuvelier B, Fernandez H. Fertility after ectopic pregnancy: first results of a population-based cohort study in France. Hum Reprod 1996;11:99–104. [4] Marcus SF, Brindsen PR. Analysis of the incidence and risk factors
P. Mock et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 94 (2001) 155 – 157
[5] [6]
[7]
[8]
[9]
associated with ectopic pregnancy following in-vitro fertilization and embryo transfer. Hum Reprod 1995;6:995–8. De Graaf FL, Demetroulis C. Bilateral tubal ectopic pregnancy: diagnostic pitfalls. Br J Clin Pract 1997;51:56–8. Hewitt J, Martin R, Steptoe PC, Rowland GF, Webster J. Bilateral tubal ectopic pregnancy following IVF and embryo replacement. Br J Obstet Gynaecol 1987;92:850–2. Aanesen A, Flam F. Bilateral tubal pregnancy following in vitro fertilization and transfer of two embryos. Eur J Obstet Gynecol Reprod Biol 1996;64:235–6. Kahraman S, Alatas C, Tasdemir M, Nuhoglu A, Aksoy S, Biberoglu K. Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection. Hum Reprod 1995;10:3020–1. Fernandez H, Lelaidier C, Thouvenez V, Frydman R. The use of a
[10]
[11] [12]
[13]
157
pretherapeutic, predictive score to determine inclusion criteria for the non-surgical treatment of ectopic pregnancy. Hum Reprod 1991;6:995–8. Hughes JN, Olszewska B, Dauvergne P, Bulwa S, Cedrin-Durnerin I. Two-step diagnosis of bilateral ectopic pregnancy after in vitro fertilization. J Assist Reprod Genet 1995;12:460–2. Timor-Tritsch IE, Rottem S. Transvaginal sonographic study of the fallopian tube. Obstet Gynecol 1987;70:424–8. Brown DL, Felker RE, Stovall TG et al. Serial endovaginal sonography of ectopic pregnancies treated with methotrexate. Obstet Gynecol 1991;77:406–9. Hajenius PJ et al. Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Lancet 1997;350:774–9.
www.elsevier.com / locate / ejogrb
Case report
Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection treated by conservative medical treatment Interest of sonographic follow-up Pascal Mock*, Franc¸ois Olivennes, Severin Doumerc, Rene´ Frydman, Herve´ Fernandez ˆ ´ ` , Clamart, France Antoine Beclere Department of Obstetrics and Gynaecology and Reproductive Endocrinology, Hopital Received 30 November 1999; accepted 23 February 2000
Abstract We describe a case of early bilateral tubal pregnancy diagnosed by transvaginal ultrasonography after intracytoplasmic sperm injection (ICSI) and embryo transfer (ET). A follow-up by transvaginal sonography was done with a systematic second scan (5 days) after the first diagnosis of left tubal ectopic pregnancy in case of assisted conception procedure. This follow-up sonographic strategy permitted us to perform a conservative treatment for this case of spontaneous bilateral tubal pregnancy by two consecutive (left then right) in-situ methotrexate injections under vaginal ultrasonographic guidance without any complications. 2001 Elsevier Science Ireland Ltd. All rights reserved. Keywords: Ectopic pregnancy; ICSI; Sonography
1. Introduction The incidence of ectopic pregnancy has tripled in the Western World over the past two decades, with a plateauing for the last 10 years as recently shown in the USA [1,2]. In France, it has been estimated to 2% of births [3] and unusual forms of ectopic pregnancy such as simultaneous bilateral tubal implantation are becoming more frequent in particular after in vitro fertilization and embryo transfer (IVF–ET) [4,5]. The diagnosis of bilateral ectopic pregnancy after IVF– ET is difficult and usually performed belatedly by laparoscopy or laparotomy when haemorrhagic complication appears [6,7]. Recently, it was described after IVF–ET and intracytoplasmic sperm injection with a complicated clini-
cal presentation (unilateral tubal rupture) requiring radical surgical procedure by laparoscopy [8]. We describe a case of early bilateral tubal pregnancy diagnosed by transvaginal ultrasonography after ICSI / ET. We were able to perform a medical treatment by two consecutive in-situ methotrexate injections under vaginal ultrasonographic guidance because of an uncomplicated clinical presentation. The present report demonstrates that an early diagnosis of simultaneous bilateral tubal pregnancy is possible when a follow-up by transvaginal sonography with a systematic second scan is proposed systematically in case of assisted conception procedure.
2. Case report ´ ´ et d’Endocrinologie *Corresponding author. Clinique de Sterilite ´ ` 14, Switzerland. Tel.: 141-22-382Gynecologique, HUG, 1211 Geneve 4331; fax: 141-22-382-4310. E-mail address: [email protected] (P. Mock).
A 33-year-old woman with a history of two implantation failures after intracytoplasmic sperm injection (ICSI) for oligo-astheno-teratospermia was enrolled in a third attempt with assisted hatching. A laparoscopy performed less than
0301-2115 / 01 / $ – see front matter 2001 Elsevier Science Ireland Ltd. All rights reserved. PII: S0301-2115( 00 )00315-8
156
P. Mock et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 94 (2001) 155 – 157
6 months before was normal. We proceeded to a new cycle of controlled ovarian stimulation with a single injection of a time-release GnRH (Decapeptyl; Ipsen, Paris, France) 3 mg i.m. (administered on day 2 of the menstrual cycle) followed by administration of human menopausal gonadotropin (Humegon; Organon, Saint-Denis, France). Triggering of ovulation was obtained with hCG (Gonadotrophine Chorionic ‘Endo’, Organon, 10,000 IU, i.m.) administered on criteria of follicular maturation determined by ultrasound and estradiol (E2) findings. Four embryos were transferred transcervically using Frydman’s catheter on day 3. Luteal phase was supported with 300 mg of micronized progesterone (Utrogestan, Besins-Iscovesco Pharmaceuticals, Paris, France) administered daily (100 mg in the morning, 200 mg in the evening) by vaginal route starting on the evening of the ET day. Thirty days later the first transvaginal sonography was performed with a hCG serum level at 1321 mIU / ml. At this time, an asymptomatic left ectopic pregnancy was detected with sonographic pictures of mixed echoid pattern at the left adnexial region measuring 34 mm without intra-abdominal fluid collection. This case allowed us to propose a conservative medical treatment since a low score was calculated (511) according to previously defined criteria [9]. We therefore proceeded to an ultrasound-guided in-situ injection of methotrexate (MTX) (1 mg / kg) using a 22gauge needle. Five days later, a new control by transvaginal scan was required as usual for a pregnancy obtained by IVF / ET. We diagnosed a new tubal pregnancy on the other right side with an endovaginal ultrasound examination showing a latero-uterine mass of 19315 mm (serum hCG51537 mIU / ml and 1724 mIU / ml 3 days before). Similarly, because of a low score (10) we performed a new in situ MTX injection (1 mg / kg) under sonographic guidance. The postoperative period remained uneventful with hCG levels returned to below 10 mIU / ml 34 days after the first injection.
3. Discussion This case illustrates that an early diagnosis of bilateral tubal pregnancy is possible by using a transvaginal ultrasonography follow-up strategy. Indeed, in the present case report, a second scan 5 days after the initial EP diagnosis on the right side showed a contralateral tubal pregnancy before any complication. As mentioned recently, its diagnosis may be difficult because of a delayed controlateral tubal pregnancy with an overlook during the first laparoscopy [10]. It is interesting to note that similarly the diagnosis by scan was made in two steps with a delay of 5 days as if the natural history of both pregnancies was different. Whereas it is well accepted that transvaginal sonography changed the diagnostic algorithm of ectopic pregnancy with an earlier diagnosis [11], its use for the follow-up of
medically treated EP such as local or intramuscular MTX injection is of no benefit in the management of these patients, because the ectopic mass usually increased in size with an amount of fluid in the Douglas cul-de-sac increasing [12]. Therefore, ultrasound is performed only in cases of abnormal clinical signs (pelvic pain) or hCG clearance alterations with increasing or plateauing levels. However, a careful inspection of the controlateral tube may be a very interesting indication compared to other tools such as laparoscopy to avoid complications such as secondary tubal rupture. Furthermore, an early diagnosis of bilateral ectopic pregnancy after embryo transfer may improve the opportunity to perform a medical treatment because of uncomplicated clinical presentation. Indeed, several authors demonstrated that conservative treatment such as intramuscular MTX injection permits a similar fertility rate compared to surgical treatment [13]. Our policy of EP treatment is to perform a conservative treatment with in-situ MTX treatment when it is possible because we are convinced that such a treatment is economically more interesting with a lower cost and a similar rate of fertility. Such a policy, in our view, should similarly be applied to EP after assisted reproductive technology such as IVF. Moreover, routine use of transvaginal sonography for the follow-up of EP following IVF or ICSI may prevent delay in such a threatened diagnosis, less by evaluating the evolution of tubal lesion than through carefully examining and ruling out controlateral tubal pregnancy or intrauterine pregnancy (heterotopic pregnancy) [9]. When ectopic pregnancy is medically or surgically treated, we propose to perform, with a delay of less than 1 week, a systematic second sonography as proposed after IUP to exclude heterotopic pregnancy. Indeed, most often, the controlateral EP is asymptomatic or difficult to differentiate from the pelvic pain secondary to controlled ovarian hyperstimulation or to the medical treatment. In conclusion, the purpose of this case report is not to describe the first medical treatment of bilateral ectopic pregnancy, but to demonstrate the importance in assisted medical procedures to perform routinely a second sonographic control after the first pregnancy localisation, either intrauterine or ectopic.
References [1] Nederlof KP, Lawson HW, Saftlas AF, Atrash HK, Finch EL. Ectopic pregnancy surveillance, United States, 1970–1987. MMWR 1990;39:9. [2] Centers for Disease Control. Ectopic pregnancy, United States, 1988–1989. MMWR 1992;41:591. [3] Job-Spira N, Bouyer J, Pouly JL, Germain E, Coste J, AubletCuvelier B, Fernandez H. Fertility after ectopic pregnancy: first results of a population-based cohort study in France. Hum Reprod 1996;11:99–104. [4] Marcus SF, Brindsen PR. Analysis of the incidence and risk factors
P. Mock et al. / European Journal of Obstetrics & Gynecology and Reproductive Biology 94 (2001) 155 – 157
[5] [6]
[7]
[8]
[9]
associated with ectopic pregnancy following in-vitro fertilization and embryo transfer. Hum Reprod 1995;6:995–8. De Graaf FL, Demetroulis C. Bilateral tubal ectopic pregnancy: diagnostic pitfalls. Br J Clin Pract 1997;51:56–8. Hewitt J, Martin R, Steptoe PC, Rowland GF, Webster J. Bilateral tubal ectopic pregnancy following IVF and embryo replacement. Br J Obstet Gynaecol 1987;92:850–2. Aanesen A, Flam F. Bilateral tubal pregnancy following in vitro fertilization and transfer of two embryos. Eur J Obstet Gynecol Reprod Biol 1996;64:235–6. Kahraman S, Alatas C, Tasdemir M, Nuhoglu A, Aksoy S, Biberoglu K. Simultaneous bilateral tubal pregnancy after intracytoplasmic sperm injection. Hum Reprod 1995;10:3020–1. Fernandez H, Lelaidier C, Thouvenez V, Frydman R. The use of a
[10]
[11] [12]
[13]
157
pretherapeutic, predictive score to determine inclusion criteria for the non-surgical treatment of ectopic pregnancy. Hum Reprod 1991;6:995–8. Hughes JN, Olszewska B, Dauvergne P, Bulwa S, Cedrin-Durnerin I. Two-step diagnosis of bilateral ectopic pregnancy after in vitro fertilization. J Assist Reprod Genet 1995;12:460–2. Timor-Tritsch IE, Rottem S. Transvaginal sonographic study of the fallopian tube. Obstet Gynecol 1987;70:424–8. Brown DL, Felker RE, Stovall TG et al. Serial endovaginal sonography of ectopic pregnancies treated with methotrexate. Obstet Gynecol 1991;77:406–9. Hajenius PJ et al. Randomised trial of systemic methotrexate versus laparoscopic salpingostomy in tubal pregnancy. Lancet 1997;350:774–9.