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Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy
FERTILITY AND STERILITY
Vol. 50, No.6, December 1988
Copyright If) 1988 The American Fertility Society
Printed in U.S.A.
Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy
Bruce Patsner, M.D.* Daniel Kenigsberg, M.D. Department of Obstetrics and Gynecology, State University of New York (SUNY) at Stony Brook, School of Medicine, Stony Brook, New York
Conservative surgery for unruptured ectopic pregnancy has improved subsequent pregnancy rates and decreased operative morbidity. However, the persistence of trophoblastic tissue following such surgery may complicate the postoperative recovery and, if serial serum human chorionic gonadotrophin levels continue to rise, may ultimately require laparoscopy, which mayor may not be able to identify the residual ectopic. When the source of rising hCG after conservative tubal surgery is not identified during subsequent second-look laparoscopy, methotrexate (Amethopterin) may be employed to eradicate residual trophoblast. Intravenous methotrexate with citrovorum factor rescue was first used to treat a small, interstitial un ruptured ectopic pregnancy by Tanaka 1 in 1982, and parenteral methotrexate plus citrovorum factor later reported by Cowan 2 to successfully treat persistent ectopic pregnancy following manual expression of a small, ampullary ectopic. Ory 3 subsequently used parenteral methotrexate therapy without citrovorum factor to treat small, unruptured ampullary ectopic pregnancy in six patients, with cure in five of six patients. Outpatient oral methotrexate therapy without citrovorum factor has not been previously reported for treatment of persistent or unruptured ectopic pregnancy. The present case is the first reported use of oral methotrexate therapy alone on an ambulatory basis to treat persistent ectopic pregnancy following conservative tubal surgery. Received June 8, 1988; revised and accepted August 9, 1988.
* Reprint requests: Bruce Patsner, M.D., Department of Obstetrics and Gynecology, SUNY School of Medicine, Health Sciences Center, Stony Brook, New York 11794 1/3091.
982
Patsner and Kenigsberg
Communications-in-brief
CASE REPORT
A 24-year-old gravida 2 para 0, last menstrual period (LMP) March 5, 1988, was admitted on April 3, 1988, with a 2-day history of increasing right lower quadrant pain, vaginal spotting, and a positive home pregnancy test. Past gynecologic histo~y was remarkable for an earlier therapeutic abortion and no history of intrauterine device use or pelvic inflammatory disease. Physical examination revealed marked lower quadrant tenderness, a normal size uterus, and right adnexal fullness. Culdocentesis was positive for unclotted blood, and serum {3-human chorionic gonadotropin ({3-hCG) was 170 mIU Iml. Exploratory laparotomy revealed a 400 cc hemoperitoneum and bilateral hydrosalpinx, with a 1.0 X 0.5 cm dilatation of the left oviduct and a right fallopian tube with a small clot aborting out of a normal-appearing fimbria. Left linear salpingostomy revealed no products of conception. Examination of the cul-de-sac and right tubal clot by pathology revealed trophoblastic villi. Postoperative course was uneventful and serum {3hCG on postoperative day 4 was 64 mIU Iml. Serial serum {3-hCG levels initially fell to 30 mIU/ml but gradually rose to 67, then 91 and 110 mIU Iml over the next 2 weeks. Vaginal spotting and vague right shoulder pain persisted, and the patient returned to the operating room on April 22, 1988. Dilatation and curettage revealed no trophoblast, and diagnostic laparoscopy was essentially negative except for a small clot in the cul-de-sac that contained no villi on microscopic examination. The diagnosis of persistent ectopic pregnancy was made, and outpatient treatment with oral Fertility and Sterility
methotrexate 0.4 mg/kg/day (25 mg/day) X 5 days was initiated. Serum (3-hCG just before starting methotrexate on May 2, 1988, was 130 mIU/ml. Complete blood count (CBC) revealed 4.4 cells/ mm 3 , hemoglobin 13.2 g%, and hematocrit 38.3%. Liver function tests were all normal. Chest x-ray was negative. Oral methotrexate was well tolerated. No change in CBC or liver function tests was noted, and stomatitis/mucusitis did not occur. Serum (3-hCG 2 days after completing methotrexate was 27 mIU / ml, and 1 week later, before the planned second course, was 5 mIU /ml. Treatment was terminated, and the patient remains asymptomatic with a serum (3-hCG of 5 mIU /ml.
DISCUSSION
Although persistent trophoblastic tissue after conservative tubal surgery for ectopic pregnancy has been successfully eradicated with use of parenteral or intravenous methotrexate with citrovorum factor rescue, both reported regimens require either hospitalization or daily visits to the physician's office and frequently are accompanied by stomatitis. Recently Barter4 reported the successful use of standard dose (0.4 mg/kg/day X 5 days) oral methotrexate therapy to treat 15 patients with nonmet-
Vol. 50, No.6, December 1988
astatic gestational trophoblastic disease. Their 87% sustained remission rate compared favorably to that obtained with conventional methotrexate therapy, with only mild mucusitis in 7 of 15 patients and no myelosuppression or hepatic toxicity. More importantly, all treatment was given on a weekly outpatient basis, without hospitalization or interference with the patient's work schedule. The present case illustrates the successful use of oral methotrexate therapy to treat persistent ectopic pregnancy after failure to identify the source at laparoscopy. Only one outpatient treatment was required, and no toxicity was noted. Additional investigation of oral methotrexate therapy for eradication of postoperative residual trophoblast seems justified based on the present report. REFERENCES 1. Tanaka T, Hayashi H, Kutsuzawa T, Fujimoto S, Ichinoe
K: Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril37:851, 1982 2. Cowan BD, McGehee RP, Bates GW: Treatment of persistent ectopic pregnancy with methotrexate and leucovorum rescue: a case report. Obstet GynecoI67:50S, 1986 . 3. Ory SJ, Villanueva AL, Sand PK, Tamura PK: Conservative treatment of ectopic pregnancy with methotrexate. Am J Obstet GynecoI154:1299, 1986 4. Barter JF, Soong SJ, Hatch KD, Orr JW, Partridge EC, Austin JM, Shingleton HM: Treatment of non-metastatic gestational trophoblastic disease with oral methotrexate. Am J Obstet GynecoI157:1l66, 1987
Patsner and Kenigsberg
Communications-in-brief
983
Vol. 50, No.6, December 1988
Copyright If) 1988 The American Fertility Society
Printed in U.S.A.
Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy
Bruce Patsner, M.D.* Daniel Kenigsberg, M.D. Department of Obstetrics and Gynecology, State University of New York (SUNY) at Stony Brook, School of Medicine, Stony Brook, New York
Conservative surgery for unruptured ectopic pregnancy has improved subsequent pregnancy rates and decreased operative morbidity. However, the persistence of trophoblastic tissue following such surgery may complicate the postoperative recovery and, if serial serum human chorionic gonadotrophin levels continue to rise, may ultimately require laparoscopy, which mayor may not be able to identify the residual ectopic. When the source of rising hCG after conservative tubal surgery is not identified during subsequent second-look laparoscopy, methotrexate (Amethopterin) may be employed to eradicate residual trophoblast. Intravenous methotrexate with citrovorum factor rescue was first used to treat a small, interstitial un ruptured ectopic pregnancy by Tanaka 1 in 1982, and parenteral methotrexate plus citrovorum factor later reported by Cowan 2 to successfully treat persistent ectopic pregnancy following manual expression of a small, ampullary ectopic. Ory 3 subsequently used parenteral methotrexate therapy without citrovorum factor to treat small, unruptured ampullary ectopic pregnancy in six patients, with cure in five of six patients. Outpatient oral methotrexate therapy without citrovorum factor has not been previously reported for treatment of persistent or unruptured ectopic pregnancy. The present case is the first reported use of oral methotrexate therapy alone on an ambulatory basis to treat persistent ectopic pregnancy following conservative tubal surgery. Received June 8, 1988; revised and accepted August 9, 1988.
* Reprint requests: Bruce Patsner, M.D., Department of Obstetrics and Gynecology, SUNY School of Medicine, Health Sciences Center, Stony Brook, New York 11794 1/3091.
982
Patsner and Kenigsberg
Communications-in-brief
CASE REPORT
A 24-year-old gravida 2 para 0, last menstrual period (LMP) March 5, 1988, was admitted on April 3, 1988, with a 2-day history of increasing right lower quadrant pain, vaginal spotting, and a positive home pregnancy test. Past gynecologic histo~y was remarkable for an earlier therapeutic abortion and no history of intrauterine device use or pelvic inflammatory disease. Physical examination revealed marked lower quadrant tenderness, a normal size uterus, and right adnexal fullness. Culdocentesis was positive for unclotted blood, and serum {3-human chorionic gonadotropin ({3-hCG) was 170 mIU Iml. Exploratory laparotomy revealed a 400 cc hemoperitoneum and bilateral hydrosalpinx, with a 1.0 X 0.5 cm dilatation of the left oviduct and a right fallopian tube with a small clot aborting out of a normal-appearing fimbria. Left linear salpingostomy revealed no products of conception. Examination of the cul-de-sac and right tubal clot by pathology revealed trophoblastic villi. Postoperative course was uneventful and serum {3hCG on postoperative day 4 was 64 mIU Iml. Serial serum {3-hCG levels initially fell to 30 mIU/ml but gradually rose to 67, then 91 and 110 mIU Iml over the next 2 weeks. Vaginal spotting and vague right shoulder pain persisted, and the patient returned to the operating room on April 22, 1988. Dilatation and curettage revealed no trophoblast, and diagnostic laparoscopy was essentially negative except for a small clot in the cul-de-sac that contained no villi on microscopic examination. The diagnosis of persistent ectopic pregnancy was made, and outpatient treatment with oral Fertility and Sterility
methotrexate 0.4 mg/kg/day (25 mg/day) X 5 days was initiated. Serum (3-hCG just before starting methotrexate on May 2, 1988, was 130 mIU/ml. Complete blood count (CBC) revealed 4.4 cells/ mm 3 , hemoglobin 13.2 g%, and hematocrit 38.3%. Liver function tests were all normal. Chest x-ray was negative. Oral methotrexate was well tolerated. No change in CBC or liver function tests was noted, and stomatitis/mucusitis did not occur. Serum (3-hCG 2 days after completing methotrexate was 27 mIU / ml, and 1 week later, before the planned second course, was 5 mIU /ml. Treatment was terminated, and the patient remains asymptomatic with a serum (3-hCG of 5 mIU /ml.
DISCUSSION
Although persistent trophoblastic tissue after conservative tubal surgery for ectopic pregnancy has been successfully eradicated with use of parenteral or intravenous methotrexate with citrovorum factor rescue, both reported regimens require either hospitalization or daily visits to the physician's office and frequently are accompanied by stomatitis. Recently Barter4 reported the successful use of standard dose (0.4 mg/kg/day X 5 days) oral methotrexate therapy to treat 15 patients with nonmet-
Vol. 50, No.6, December 1988
astatic gestational trophoblastic disease. Their 87% sustained remission rate compared favorably to that obtained with conventional methotrexate therapy, with only mild mucusitis in 7 of 15 patients and no myelosuppression or hepatic toxicity. More importantly, all treatment was given on a weekly outpatient basis, without hospitalization or interference with the patient's work schedule. The present case illustrates the successful use of oral methotrexate therapy to treat persistent ectopic pregnancy after failure to identify the source at laparoscopy. Only one outpatient treatment was required, and no toxicity was noted. Additional investigation of oral methotrexate therapy for eradication of postoperative residual trophoblast seems justified based on the present report. REFERENCES 1. Tanaka T, Hayashi H, Kutsuzawa T, Fujimoto S, Ichinoe
K: Treatment of interstitial ectopic pregnancy with methotrexate: report of a successful case. Fertil Steril37:851, 1982 2. Cowan BD, McGehee RP, Bates GW: Treatment of persistent ectopic pregnancy with methotrexate and leucovorum rescue: a case report. Obstet GynecoI67:50S, 1986 . 3. Ory SJ, Villanueva AL, Sand PK, Tamura PK: Conservative treatment of ectopic pregnancy with methotrexate. Am J Obstet GynecoI154:1299, 1986 4. Barter JF, Soong SJ, Hatch KD, Orr JW, Partridge EC, Austin JM, Shingleton HM: Treatment of non-metastatic gestational trophoblastic disease with oral methotrexate. Am J Obstet GynecoI157:1l66, 1987
Patsner and Kenigsberg
Communications-in-brief
983