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Treatment of Persistent Ectopic Pregnancy—Complications?
Letters-to-the-editor Paul G. McDonough, M.D. FERTILITY AND STERILITY
Vol. 56, No.5, November 1991
Copyright"' 1991 The American Fertility Society
Treatment of Persistent Ectopic PregnancyComplications?
To the Editor: Patsner and Kenigsberg1 reported the use of oral methotrexate therapy alone, on an ambulatory basis, for the treatment of persistent ectopic pregnancy. The article suggested this form of treatment as an alternative course of management for persistent ectopic pregnancy. Before this recommendation can be accepted, we believe it is important to report a recent experience with a similar patient at our institution. A 34-year-old patient, 1-year status posttuboplasty for bilateral hydrosalpinx and in apparent good health, was noted to have 6 weeks of amenorrhea, vaginal staining, and right lower quadrant pain for 2 days. Quantitative {3-human chorionic gonadotropin ({3-hCG) was 1,400 miU/mL. Endovaginal sonogram revealed a right adnexal mass and no intrauterine sac. An unruptured right tubal pregnancy was diagnosed and removed by laparoscopic salpingotomy. Subsequent quantitative {3-hCG levels at 10, 18, and 25 days after surgery were 186, 171, and 144 miU/mL, respectively. Persistent ectopic pregnancy was diagnosed. The option of using medical therapy was discussed with the patient and consent was obtained. The patient received methotrexate 85 mg total over 3 days before discontinuing secondary to severe side effects. (No other medication was taken during this time.) These included severe stomatitis, photophobia, a persistent headache, and an acute paronychia of the right hand. Six days after initiating treatment, an outbreak of herpetic lesions of the lip and perineum were noted. One week after therapy, {3-hCG was 42 miU/mL, serum transaminases were slightly elevated, and the complete blood count was within normal limits. After two weeks, liver function tests were within normal limits, the pregnancy test was negative, and all symptoms improved. In our patient, oral methotrexate therapy was successful in treating a persistent ectopic pregnancy but was associated with severe side effects. The morbidity associated with repeat laparoscopic intervention would likely have been less than what was encountered with methotrexate therapy. We present this case to demonstrate that the use of methotrexate is not benign treatment. Case reports give us new avenues to explore but should be taken 1004
Letters-to-the-editor
Printed on acid-free paper in U.S.A.
in context. Although the concept of medical management is good, no comparative studies of the various proposed regimen have been done. Therefore, this "alternative course of therapy" needs to be approached with caution, and we suggest a wider experience be obtained before recommending it for general use.
Marilyn Loh-Collado, M.D. Department of Obstetrics and Gynecology Richard V. Grazi, M.D. Division of Reproductive Endocrinology Maimonides Medical Center Brooklyn, New York January 14, 1991
REFERENCE 1. Patsner B, Kenigsberg D: Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy. Fertil Steril 50:982, 1988
Reply of the Authors: In response to Loh-Collado and Grazi, I would make the following comments. 1. The letter describes a case of a persistent but falling {3-human chorionic gonadotropin ({3-hCG) level 25 days after laparoscopic salpingostomy with the final {3-hCG level being 144 miU/mL (10% the preoperative value). We question the indication for any active management, medical or surgical, in such a case in the absence of symptoms or a rise in titers. Further surgical intervention and general anesthesia is not without risks. 2. The patient received methotrexate 85 mg over 3 days. The mode of administration is not mentioned, but I assume it was oral. With 25-mg increments, we are not sure how one gets to a total dose of 85 mg. Stomatitis is a common complication with methotrexate, although quite uncommon with oral therapy. Photophobia and persistent headache and skin infections are not common side effects. 3. There were herpetic lesions after initiating treatment. These can occur spontaneously in a patient with known herpes. 4. Serum transamineses were slightly elevated 1 Fertility and Sterility
week after therapy. Were prethcrapy transaminases obtained? We thank and appreciate Drs. Loh-Collado and Grazi's interest in our paper on oral methotrexate. Since its publication in 1988, much has been learned about the expectant and medical therapy of ectopic pregnancies. 1•2 The sum of this experience, to date, is that it can take several months for an ectopic pregnancy to completely resolve to the level of negative {j-hCG levels after medical therapy. Furthermore, methotrexate side effects do occur in a small proportion of the patients treated with this agent for complete trophoblastic obliteration.
Daniel Kenigsberg, M.D. Bruce Patsner, M.D. Long Island IVF Port Jefferson, New York August 1, 1991
REFERENCES 1. Stovall TG, Ling FW, Gray LA, Carson SA, Buster JE:
Methotrexate treatment of unruptured ectopic pregnancy: a preliminary report of 100 cases. Obstet Gynecol 77:749, 1991 2. Vermesh M: Conservative management of ectopic gestation. Fertil Steril 51:559, 1989
H. Courtenay Clarke, M.D. Hotel Dieu Hospital Windsor, Ontario, Canada April18, 1991
REFERENCES 1. Cook AS, Rock JA: The role of laparoscopy in the treatment
of endometriosis. Fertil Steril 55:663, 1991 2. Clarke HC: Laparoscopy-new instruments for suturing and ligation. Fertil Steril 23:274, 1972 3. Reich H, McGlynn F, Budin R: Laparoscopic repair of fullthickness bowel injury. J Laparoendoscopic Surg 1:119, 1991
Reply of the Authors: We acknowledge Dr. Clarke's contribution and appreciate his comments on loop ligation in laparoscopy.
Andrew S. Cook, M.D. John A. Rock, M.D. Department of Gynecology and Obstetrics The Johns Hopkins University School of Medicine Baltimore, Maryland July 30, 1991
Value of Ultrasound-Guided Embryo Transfer Loop Ligation in Laparoscopy
To the Editor: Cook and Rock 1 have noted several technical limitations unique to laparoscopic surgery. I agree that many of these can be overcome by the skill of the surgeon and availability of proper instruments. However, for laparoscopic salpingectomy and oophorectomy they offer loop ligation using multiple endoloop sutures. Suturing and loop ligation by laparoscopy were procedures described by me in 1972 in Fertility and Sterility, 2 initiating operative laparoscopy. I described a simple ligator (knot-pusher) and suturing needle forceps and applied them for similar procedures. Unlike the endoloop suture, with these reusable instruments the surgeon can apply various forms of knots, change suture type at his/her discretion, and maintain continuous control in suturing. They are now being rediscovered. 3 These instruments provide the more strict adherence to the principles of good surgical technique that Cook and Rock seek in their paper. Vol. 56, No.5, November 1991
To the Editor: In the report by Hurley et al., 1 the authors claim to have obtained higher pregnancy rates by ultrasound-guided embryo transfer (ET), at least in the patients in which a single embryo was transferred. According to the authors, the recognition of congenital uterine abnormalities at the time of transfer is another advantage of this technique. We would applaud an innovative technique of ET that could improve the results of in vitro fertilization (IVF), but we believe the conclusions from this study are statistically ill founded and hence, we consider the advice to guide the transfer of a single embryo by transvaginal ultrasound at least premature. Even if statistically correct, the comparison of pregnancy rates of 1/45 and 4/23 in the single transfer group is very thin ground to stand on. Because no information was provided about the statistical method used, we applied the exact Fisher test to the data provided and found P to be 0.041 instead of P < 0.01 as reported in the article. In the subgroup of patients in which three embryos were transferred, the authors found the ultrasound-guided Letters-to-the-editor
1005
Vol. 56, No.5, November 1991
Copyright"' 1991 The American Fertility Society
Treatment of Persistent Ectopic PregnancyComplications?
To the Editor: Patsner and Kenigsberg1 reported the use of oral methotrexate therapy alone, on an ambulatory basis, for the treatment of persistent ectopic pregnancy. The article suggested this form of treatment as an alternative course of management for persistent ectopic pregnancy. Before this recommendation can be accepted, we believe it is important to report a recent experience with a similar patient at our institution. A 34-year-old patient, 1-year status posttuboplasty for bilateral hydrosalpinx and in apparent good health, was noted to have 6 weeks of amenorrhea, vaginal staining, and right lower quadrant pain for 2 days. Quantitative {3-human chorionic gonadotropin ({3-hCG) was 1,400 miU/mL. Endovaginal sonogram revealed a right adnexal mass and no intrauterine sac. An unruptured right tubal pregnancy was diagnosed and removed by laparoscopic salpingotomy. Subsequent quantitative {3-hCG levels at 10, 18, and 25 days after surgery were 186, 171, and 144 miU/mL, respectively. Persistent ectopic pregnancy was diagnosed. The option of using medical therapy was discussed with the patient and consent was obtained. The patient received methotrexate 85 mg total over 3 days before discontinuing secondary to severe side effects. (No other medication was taken during this time.) These included severe stomatitis, photophobia, a persistent headache, and an acute paronychia of the right hand. Six days after initiating treatment, an outbreak of herpetic lesions of the lip and perineum were noted. One week after therapy, {3-hCG was 42 miU/mL, serum transaminases were slightly elevated, and the complete blood count was within normal limits. After two weeks, liver function tests were within normal limits, the pregnancy test was negative, and all symptoms improved. In our patient, oral methotrexate therapy was successful in treating a persistent ectopic pregnancy but was associated with severe side effects. The morbidity associated with repeat laparoscopic intervention would likely have been less than what was encountered with methotrexate therapy. We present this case to demonstrate that the use of methotrexate is not benign treatment. Case reports give us new avenues to explore but should be taken 1004
Letters-to-the-editor
Printed on acid-free paper in U.S.A.
in context. Although the concept of medical management is good, no comparative studies of the various proposed regimen have been done. Therefore, this "alternative course of therapy" needs to be approached with caution, and we suggest a wider experience be obtained before recommending it for general use.
Marilyn Loh-Collado, M.D. Department of Obstetrics and Gynecology Richard V. Grazi, M.D. Division of Reproductive Endocrinology Maimonides Medical Center Brooklyn, New York January 14, 1991
REFERENCE 1. Patsner B, Kenigsberg D: Successful treatment of persistent ectopic pregnancy with oral methotrexate therapy. Fertil Steril 50:982, 1988
Reply of the Authors: In response to Loh-Collado and Grazi, I would make the following comments. 1. The letter describes a case of a persistent but falling {3-human chorionic gonadotropin ({3-hCG) level 25 days after laparoscopic salpingostomy with the final {3-hCG level being 144 miU/mL (10% the preoperative value). We question the indication for any active management, medical or surgical, in such a case in the absence of symptoms or a rise in titers. Further surgical intervention and general anesthesia is not without risks. 2. The patient received methotrexate 85 mg over 3 days. The mode of administration is not mentioned, but I assume it was oral. With 25-mg increments, we are not sure how one gets to a total dose of 85 mg. Stomatitis is a common complication with methotrexate, although quite uncommon with oral therapy. Photophobia and persistent headache and skin infections are not common side effects. 3. There were herpetic lesions after initiating treatment. These can occur spontaneously in a patient with known herpes. 4. Serum transamineses were slightly elevated 1 Fertility and Sterility
week after therapy. Were prethcrapy transaminases obtained? We thank and appreciate Drs. Loh-Collado and Grazi's interest in our paper on oral methotrexate. Since its publication in 1988, much has been learned about the expectant and medical therapy of ectopic pregnancies. 1•2 The sum of this experience, to date, is that it can take several months for an ectopic pregnancy to completely resolve to the level of negative {j-hCG levels after medical therapy. Furthermore, methotrexate side effects do occur in a small proportion of the patients treated with this agent for complete trophoblastic obliteration.
Daniel Kenigsberg, M.D. Bruce Patsner, M.D. Long Island IVF Port Jefferson, New York August 1, 1991
REFERENCES 1. Stovall TG, Ling FW, Gray LA, Carson SA, Buster JE:
Methotrexate treatment of unruptured ectopic pregnancy: a preliminary report of 100 cases. Obstet Gynecol 77:749, 1991 2. Vermesh M: Conservative management of ectopic gestation. Fertil Steril 51:559, 1989
H. Courtenay Clarke, M.D. Hotel Dieu Hospital Windsor, Ontario, Canada April18, 1991
REFERENCES 1. Cook AS, Rock JA: The role of laparoscopy in the treatment
of endometriosis. Fertil Steril 55:663, 1991 2. Clarke HC: Laparoscopy-new instruments for suturing and ligation. Fertil Steril 23:274, 1972 3. Reich H, McGlynn F, Budin R: Laparoscopic repair of fullthickness bowel injury. J Laparoendoscopic Surg 1:119, 1991
Reply of the Authors: We acknowledge Dr. Clarke's contribution and appreciate his comments on loop ligation in laparoscopy.
Andrew S. Cook, M.D. John A. Rock, M.D. Department of Gynecology and Obstetrics The Johns Hopkins University School of Medicine Baltimore, Maryland July 30, 1991
Value of Ultrasound-Guided Embryo Transfer Loop Ligation in Laparoscopy
To the Editor: Cook and Rock 1 have noted several technical limitations unique to laparoscopic surgery. I agree that many of these can be overcome by the skill of the surgeon and availability of proper instruments. However, for laparoscopic salpingectomy and oophorectomy they offer loop ligation using multiple endoloop sutures. Suturing and loop ligation by laparoscopy were procedures described by me in 1972 in Fertility and Sterility, 2 initiating operative laparoscopy. I described a simple ligator (knot-pusher) and suturing needle forceps and applied them for similar procedures. Unlike the endoloop suture, with these reusable instruments the surgeon can apply various forms of knots, change suture type at his/her discretion, and maintain continuous control in suturing. They are now being rediscovered. 3 These instruments provide the more strict adherence to the principles of good surgical technique that Cook and Rock seek in their paper. Vol. 56, No.5, November 1991
To the Editor: In the report by Hurley et al., 1 the authors claim to have obtained higher pregnancy rates by ultrasound-guided embryo transfer (ET), at least in the patients in which a single embryo was transferred. According to the authors, the recognition of congenital uterine abnormalities at the time of transfer is another advantage of this technique. We would applaud an innovative technique of ET that could improve the results of in vitro fertilization (IVF), but we believe the conclusions from this study are statistically ill founded and hence, we consider the advice to guide the transfer of a single embryo by transvaginal ultrasound at least premature. Even if statistically correct, the comparison of pregnancy rates of 1/45 and 4/23 in the single transfer group is very thin ground to stand on. Because no information was provided about the statistical method used, we applied the exact Fisher test to the data provided and found P to be 0.041 instead of P < 0.01 as reported in the article. In the subgroup of patients in which three embryos were transferred, the authors found the ultrasound-guided Letters-to-the-editor
1005