Human Reproduction vol.6 no.2 pp.302-306, 1991
The place of methotrexate in the management of interstitial pregnancy
Herve" Fernandez1, Dominique De Ziegler, Phillipe Bourget2, Pierre Feltain and Ren£ Frydman Department of Obstetrics and Gynaecology, Hdpital Antoine Beclere, 157 rue de la Porte de Trivaux, 92141 Clamart and 2 Laboratory of Pharmacology and Toxicology, Hdpital Antoine Berclere, 157 rue de la Porte de Trivaux, 92141 Clamart, France 'To whom correspondence should be addressed
Six patients with interstitial pregnancies were treated with systemic or local injections of methotrexate, 15 mg i.m. daily for 5 days, or 1 mg/kg for 1 day. One dose of folinic acid rescue (50 mg) was administered on the first day of the treatment course. Diagnosis of interstitial pregnancy was established either by laparoscopy or transvaginal ultrasound. Out of six patients, five had serial measurements of serum human chorionk gonadotrophin (HCG), progesterone (P) and 17/3-oestradiol (Ej) until either the ectopic pregnancy resolved or surgery was performed. For one patient operated on day 1 after medical treatment, no serial serum measurements were performed. Serum HCG became undetectable under medical treatment in only four of the six patients. Out of these four patients, three had an initial level of HCG < 1000 mlU/ml. Two patients underwent surgery (salpingectomy) because either the level of serum HCG did not decrease after the course of methotrexate therapy or it was required the next day to stop haemorrhage. In these patients, the initial level of HCG at the time of diagnosis, was 5300 and 43 000 mlU/ml, respectively. In the four patients who received conservative medical treatment only, the next menstrual period occurred 20—46 days after the onset of methotrexate and was preceded by luteal activity. A control hysterosalpingography performed 2 months later showed that in the four patients who received medical treatment only, the Fallopian tube was patent, and three became pregnant within 1 year of the methotrexate therapy. One of two patients who failed to respond to medical treatment and required surgical treatment, became pregnant 6 months later. Our results suggest that methotrexate is a viable alternative to surgery for interstitial pregnancies. When the initial level of serum HCG is < 1000 mlU/ml, the chances that medical treatment will succeed are increased. This suggests therefore that conservative management of interstitial pregnancies with methotrexate can be considered in selected cases, as is currently the position for the more common tubal pregnancies. Key words: interstitial pregnancy/methotrexate
302
Introduction Conservative management of ectopic pregnancies in an effort to preserve fertility is increasingly popular. Several authors have proposed the use of methotrexate as an adjunct to expectative management in order to hasten the involution of the ectopic trophoblast. Interstitial pregnancy is a rare variety of ectopic pregnancy. Its surgical management differs from other ectopic pregnancies in that removal of the ectopic trophoblast under laparoscopic guidance is impossible. Consequently the conservative management of interstitial pregnancies is a particularly attractive method. This report deals with six cases of interstitial pregnancy in which conservative treatment with methotrexate was attempted. Serial measurements of human chorionic gonadotrophin (HCG), 17/3-oestradiol (E2) and progesterone (P) were conducted in order to monitor trophoblastic and ovarian activity. The place of methotrexate in the management of interstitial pregnancies will be discussed in the light of our results and of published data. Material and methods Between March 1st 1988 and March 30th 1989, six patients with interstitial pregnancy were treated conservatively with methotrexate (MTX). The diagnosis was established either by laparoscopy or by transvaginal ultrasound. MTX was administered under three different protocols. MTX 1 protocol: 15 mg per day of MTX were administered i.m. during 5 days (duration of one course) as described by Tanaka et al. (1982). A 48-h wash-out period was allowed between two successive courses. MTX 2 protocol: 1 mg/kg/day 4 of MTX was administered i.m. on days 1, 3, 5, 7 as described by Rodi et al. (1986). MTX 3 protocol: the same as MTX 2 except on day one 1 mg/kg of MTX was injected in the gestational sac under vagino-sonography. MTX2 and MTX3 protocols were based on body weight as is usual for cytotoxic agents. Citrovorum factors were given as described by Tanaka et al. (1982) and Rodi et al. (1986) to prevent possible MTX adverse effects. Folinic acid (50 mg) was administered on the first day of each course in the MTX1 protocol. Folinic acid (0.1 mg/kg) was administered i.m. on days 2, 4, 6 and 8 for both MTX2 and MTX3 protocols. The choice of protocol type was based on literature analysis (Tanaka etal., 1982; Rodi et al., 1986). Serum HCG (RIA-GNOST-HCG: Behring, Marburg, FRG) was measured every 1 —3 days, starting at the time of diagnosis (day 0) until either spontaneous resolution occurred (serum level of HCG 200 pg/ml and progesterone > 2 ng/ml (Sauer et ai, 1987a; Spirtos et al., 1987). Red and white blood cell counts and liver function tests were also evaluated twice weekly. All the patients were fully informed of the possibility of treatment failure and of the possible need for surgical termination of their interstitial pregnancy. A control hysterosalpingogram was performed after resolution of interstitial pregnancy, in patients receiving medical treatment. Table I summarizes the presentation and management of the six patients reported below. Case report no. 1 For this West India women, a pelvic ultrasound showed a complex mass on the right side of the uterus. A diagnostic laparoscopy could not positively identify an ectopic pregnancy. Thus, a dilatation and curettage were performed with the diagnosis of miscarriage. Initially, HCG fell to a nadir of 166 mlU/ml within 5 days and then increased to 324 mlU/ml 3 days later. In view of the rising level of HCG, and after an ultrasound examination excluded a developing intrauterine gestation, a hystero-salpingography was performed which revealed a filled defect in the intramural segment of the right tube, which was attributed to an interstitial pregnancy. After the MTX 1 therapy (three courses), the level of HCG decrease to < 2 mlU/ml 20 days later. Case report no. 2 The Caucasian women presented with vaginal bleeding and a pelvic ultrasound showed an empty uterus. A laparoscopy revealed an interstitial pregnancy on the left side with a blockage of the left tube confirmed by chromohydrotubation while the right tube was patent. The MTX 2 protocol caused the HCG level to drop to
The place of methotrexate in the management of interstitial pregnancy
Herve" Fernandez1, Dominique De Ziegler, Phillipe Bourget2, Pierre Feltain and Ren£ Frydman Department of Obstetrics and Gynaecology, Hdpital Antoine Beclere, 157 rue de la Porte de Trivaux, 92141 Clamart and 2 Laboratory of Pharmacology and Toxicology, Hdpital Antoine Berclere, 157 rue de la Porte de Trivaux, 92141 Clamart, France 'To whom correspondence should be addressed
Six patients with interstitial pregnancies were treated with systemic or local injections of methotrexate, 15 mg i.m. daily for 5 days, or 1 mg/kg for 1 day. One dose of folinic acid rescue (50 mg) was administered on the first day of the treatment course. Diagnosis of interstitial pregnancy was established either by laparoscopy or transvaginal ultrasound. Out of six patients, five had serial measurements of serum human chorionk gonadotrophin (HCG), progesterone (P) and 17/3-oestradiol (Ej) until either the ectopic pregnancy resolved or surgery was performed. For one patient operated on day 1 after medical treatment, no serial serum measurements were performed. Serum HCG became undetectable under medical treatment in only four of the six patients. Out of these four patients, three had an initial level of HCG < 1000 mlU/ml. Two patients underwent surgery (salpingectomy) because either the level of serum HCG did not decrease after the course of methotrexate therapy or it was required the next day to stop haemorrhage. In these patients, the initial level of HCG at the time of diagnosis, was 5300 and 43 000 mlU/ml, respectively. In the four patients who received conservative medical treatment only, the next menstrual period occurred 20—46 days after the onset of methotrexate and was preceded by luteal activity. A control hysterosalpingography performed 2 months later showed that in the four patients who received medical treatment only, the Fallopian tube was patent, and three became pregnant within 1 year of the methotrexate therapy. One of two patients who failed to respond to medical treatment and required surgical treatment, became pregnant 6 months later. Our results suggest that methotrexate is a viable alternative to surgery for interstitial pregnancies. When the initial level of serum HCG is < 1000 mlU/ml, the chances that medical treatment will succeed are increased. This suggests therefore that conservative management of interstitial pregnancies with methotrexate can be considered in selected cases, as is currently the position for the more common tubal pregnancies. Key words: interstitial pregnancy/methotrexate
302
Introduction Conservative management of ectopic pregnancies in an effort to preserve fertility is increasingly popular. Several authors have proposed the use of methotrexate as an adjunct to expectative management in order to hasten the involution of the ectopic trophoblast. Interstitial pregnancy is a rare variety of ectopic pregnancy. Its surgical management differs from other ectopic pregnancies in that removal of the ectopic trophoblast under laparoscopic guidance is impossible. Consequently the conservative management of interstitial pregnancies is a particularly attractive method. This report deals with six cases of interstitial pregnancy in which conservative treatment with methotrexate was attempted. Serial measurements of human chorionic gonadotrophin (HCG), 17/3-oestradiol (E2) and progesterone (P) were conducted in order to monitor trophoblastic and ovarian activity. The place of methotrexate in the management of interstitial pregnancies will be discussed in the light of our results and of published data. Material and methods Between March 1st 1988 and March 30th 1989, six patients with interstitial pregnancy were treated conservatively with methotrexate (MTX). The diagnosis was established either by laparoscopy or by transvaginal ultrasound. MTX was administered under three different protocols. MTX 1 protocol: 15 mg per day of MTX were administered i.m. during 5 days (duration of one course) as described by Tanaka et al. (1982). A 48-h wash-out period was allowed between two successive courses. MTX 2 protocol: 1 mg/kg/day 4 of MTX was administered i.m. on days 1, 3, 5, 7 as described by Rodi et al. (1986). MTX 3 protocol: the same as MTX 2 except on day one 1 mg/kg of MTX was injected in the gestational sac under vagino-sonography. MTX2 and MTX3 protocols were based on body weight as is usual for cytotoxic agents. Citrovorum factors were given as described by Tanaka et al. (1982) and Rodi et al. (1986) to prevent possible MTX adverse effects. Folinic acid (50 mg) was administered on the first day of each course in the MTX1 protocol. Folinic acid (0.1 mg/kg) was administered i.m. on days 2, 4, 6 and 8 for both MTX2 and MTX3 protocols. The choice of protocol type was based on literature analysis (Tanaka etal., 1982; Rodi et al., 1986). Serum HCG (RIA-GNOST-HCG: Behring, Marburg, FRG) was measured every 1 —3 days, starting at the time of diagnosis (day 0) until either spontaneous resolution occurred (serum level of HCG 200 pg/ml and progesterone > 2 ng/ml (Sauer et ai, 1987a; Spirtos et al., 1987). Red and white blood cell counts and liver function tests were also evaluated twice weekly. All the patients were fully informed of the possibility of treatment failure and of the possible need for surgical termination of their interstitial pregnancy. A control hysterosalpingogram was performed after resolution of interstitial pregnancy, in patients receiving medical treatment. Table I summarizes the presentation and management of the six patients reported below. Case report no. 1 For this West India women, a pelvic ultrasound showed a complex mass on the right side of the uterus. A diagnostic laparoscopy could not positively identify an ectopic pregnancy. Thus, a dilatation and curettage were performed with the diagnosis of miscarriage. Initially, HCG fell to a nadir of 166 mlU/ml within 5 days and then increased to 324 mlU/ml 3 days later. In view of the rising level of HCG, and after an ultrasound examination excluded a developing intrauterine gestation, a hystero-salpingography was performed which revealed a filled defect in the intramural segment of the right tube, which was attributed to an interstitial pregnancy. After the MTX 1 therapy (three courses), the level of HCG decrease to < 2 mlU/ml 20 days later. Case report no. 2 The Caucasian women presented with vaginal bleeding and a pelvic ultrasound showed an empty uterus. A laparoscopy revealed an interstitial pregnancy on the left side with a blockage of the left tube confirmed by chromohydrotubation while the right tube was patent. The MTX 2 protocol caused the HCG level to drop to
