Medical vs. Surgical Management of Early Pregnancy Failure
http://www.100md.com
《新英格兰医药杂志》
To the Editor: The article by Zhang et al. (Aug. 25 issue)1 demonstrated the usefulness of treatment of early pregnancy failure with intravaginal misoprostol but did not describe the serious complications that can arise from such administration of this drug. Although endometritis requiring hospitalization was rare in the study by Zhang et al., the Centers for Disease Control and Prevention2 and Fischer et al. (in this issue of the Journal)3 have reported that five women died of toxic shock after endometrial infection with Clostridium sordellii in the United States and Canada after medical abortions with mifepristone and intravaginal misoprostol.
Ken-ichi Shukunami, M.D.
Koji Nishijima, M.D.
Fumikazu Kotsuji, M.D., Ph.D.
University of Fukui
Fukui 910-1193, Japan
kojigyne@fmsrsa.fukui-med.ac.jp
References
Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005;353:761-769.
Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol -- United States and Canada, 2001-2005. MMWR Morb Mortal Wkly Rep 2005;54:724-724.
Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:2352-2360.
To the Editor: Zhang et al. report that the rate of complete abortion in the misoprostol group was only 84 percent. We are concerned that the criteria used to diagnose a complete abortion were too stringent and wonder if patients who actually had a complete abortion were misclassified as having had an incomplete abortion.
Sadan et al.1 found that the false positive rate is 28.9 percent for ultrasonography in predicting retained products of conception after abortion when an endometrial thickness greater than 8 mm is used as the criterion, which is a lower cutoff than the 30 mm cited by Zhang et al. The study by Zhang et al. did not include the pathological results for the women who underwent a surgical evacuation for presumed retained products of conception after initial treatment with misoprostol. We wonder what proportion of the women who were classified as having had an incomplete abortion had negative pathological results after surgical evacuation, which would suggest a completed medical procedure. If these women were given more time, we suggest that the findings on ultrasonography would have normalized without intervention,2 possibly leading to a higher success rate for the medical regimen.
Chad A. Grotegut, M.D.
Vani Dandolu, M.D.
Temple University School of Medicine
Philadelphia, PA 19140
grotegca@tuhs.temple.edu
References
Sadan O, Golan A, Girtler O, et al. Role of sonography in the diagnosis of retained products of conception. J Ultrasound Med 2004;23:371-374.
Bar-Hava I, Aschkenazi S, Orvieto R, et al. Spectrum of normal intrauterine cavity sonographic findings after first-trimester abortion. J Ultrasound Med 2001;20:1277-1281.
The authors reply: As noted by Shukunami et al., five cases of maternal death due to toxic shock syndrome associated with C. sordellii infection have been reported after medical abortion in the United States and Canada since 2001.1,2 Clostridium species are part of normal vaginal flora and are found in the vagina of 4 to 18 percent of normal, healthy, nonpregnant women,3 though C. sordellii is a nondominant species. To date, it is unclear if these infections were related to the ascension of resident flora, to mifepristone, or to the vaginal administration of misoprostol. Thousands of women use intravaginal misoprostol for the induction of labor and medical abortion each year. Fatal C. sordellii toxic shock syndrome in such cases is extremely rare, which, in our view, is the best evidence for the safety of vaginal misoprostol. It is further noteworthy that the cited cases of medical abortion used both mifepristone (a progesterone and glucocorticoid antagonist)4 and misoprostol (a prostaglandin E1 analogue), whereas our regimen used misoprostol alone. We agree with the Food and Drug Administration advisory that physicians need to be aware of the possibility of toxic shock syndrome associated with C. sordellii infection.1 Prophylactic antibiotic use is not necessary for this indication and may even be counterproductive.1
In the study by Sadan et al. cited by Grotegut and Dandolu, 29 percent of women with an endometrial thickness greater than 8 mm after first-trimester spontaneous or induced abortion did not have retained products of conception. It is tenuous to assume that the false positive rate would remain the same for women with an endometrial thickness greater than 30 mm in our study. In fact, none of the 76 vacuum-aspiration procedures performed in the women treated with misoprostol were for the indication of an endometrial thickness exceeding 30 mm. Therefore, the success rate in our study was not affected by our criterion for endometrial thickness. We agree that endometrial thickness alone may not be a sensitive indicator of the need for vacuum aspiration, as demonstrated in our previous study.5 For the purpose of research, however, we had to set a cutoff point to standardize care within the study, thus permitting an objective estimate of efficacy.
Jun Zhang, Ph.D., M.D.
National Institute of Child Health and Human Development
Bethesda, MD 20892
zhangj@mail.nih.gov
Mitchell D. Creinin, M.D.
University of Pittsburgh
Pittsburgh, PA 15213
Kurt Barnhart, M.D., M.S.C.E.
University of Pennsylvania
Philadelphia, PA 19104
for the Management of Early Pregnancy Failure Trial Group
References
Center for Drug Evaluation and Research. FDA public health advisory: sepsis and medical abortion. Rockville, Md.: Food and Drug Administration, 2005. (Accessed November 1, 2005, at http://www.fda.gov/cder/drug/advisory/mifeprex.htm.)
Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:2352-2360.
Hammill HA. Normal vaginal flora in relation to vaginitis. Obstet Gynecol Clin North Am 1989;16:329-336.
Miech RP. Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii. Ann Pharmacother 2005;39:1483-8.
Creinin MD, Harwood B, Guido RS, Fox MC, Zhang J, NICHD Management of Early Pregnancy Failure Trial Group. Endometrial thickness after misoprostol use for early pregnancy failure. Int J Gynaecol Obstet 2004;86:22-26.
Ken-ichi Shukunami, M.D.
Koji Nishijima, M.D.
Fumikazu Kotsuji, M.D., Ph.D.
University of Fukui
Fukui 910-1193, Japan
kojigyne@fmsrsa.fukui-med.ac.jp
References
Zhang J, Gilles JM, Barnhart K, Creinin MD, Westhoff C, Frederick MM. A comparison of medical management with misoprostol and surgical management for early pregnancy failure. N Engl J Med 2005;353:761-769.
Clostridium sordellii toxic shock syndrome after medical abortion with mifepristone and intravaginal misoprostol -- United States and Canada, 2001-2005. MMWR Morb Mortal Wkly Rep 2005;54:724-724.
Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:2352-2360.
To the Editor: Zhang et al. report that the rate of complete abortion in the misoprostol group was only 84 percent. We are concerned that the criteria used to diagnose a complete abortion were too stringent and wonder if patients who actually had a complete abortion were misclassified as having had an incomplete abortion.
Sadan et al.1 found that the false positive rate is 28.9 percent for ultrasonography in predicting retained products of conception after abortion when an endometrial thickness greater than 8 mm is used as the criterion, which is a lower cutoff than the 30 mm cited by Zhang et al. The study by Zhang et al. did not include the pathological results for the women who underwent a surgical evacuation for presumed retained products of conception after initial treatment with misoprostol. We wonder what proportion of the women who were classified as having had an incomplete abortion had negative pathological results after surgical evacuation, which would suggest a completed medical procedure. If these women were given more time, we suggest that the findings on ultrasonography would have normalized without intervention,2 possibly leading to a higher success rate for the medical regimen.
Chad A. Grotegut, M.D.
Vani Dandolu, M.D.
Temple University School of Medicine
Philadelphia, PA 19140
grotegca@tuhs.temple.edu
References
Sadan O, Golan A, Girtler O, et al. Role of sonography in the diagnosis of retained products of conception. J Ultrasound Med 2004;23:371-374.
Bar-Hava I, Aschkenazi S, Orvieto R, et al. Spectrum of normal intrauterine cavity sonographic findings after first-trimester abortion. J Ultrasound Med 2001;20:1277-1281.
The authors reply: As noted by Shukunami et al., five cases of maternal death due to toxic shock syndrome associated with C. sordellii infection have been reported after medical abortion in the United States and Canada since 2001.1,2 Clostridium species are part of normal vaginal flora and are found in the vagina of 4 to 18 percent of normal, healthy, nonpregnant women,3 though C. sordellii is a nondominant species. To date, it is unclear if these infections were related to the ascension of resident flora, to mifepristone, or to the vaginal administration of misoprostol. Thousands of women use intravaginal misoprostol for the induction of labor and medical abortion each year. Fatal C. sordellii toxic shock syndrome in such cases is extremely rare, which, in our view, is the best evidence for the safety of vaginal misoprostol. It is further noteworthy that the cited cases of medical abortion used both mifepristone (a progesterone and glucocorticoid antagonist)4 and misoprostol (a prostaglandin E1 analogue), whereas our regimen used misoprostol alone. We agree with the Food and Drug Administration advisory that physicians need to be aware of the possibility of toxic shock syndrome associated with C. sordellii infection.1 Prophylactic antibiotic use is not necessary for this indication and may even be counterproductive.1
In the study by Sadan et al. cited by Grotegut and Dandolu, 29 percent of women with an endometrial thickness greater than 8 mm after first-trimester spontaneous or induced abortion did not have retained products of conception. It is tenuous to assume that the false positive rate would remain the same for women with an endometrial thickness greater than 30 mm in our study. In fact, none of the 76 vacuum-aspiration procedures performed in the women treated with misoprostol were for the indication of an endometrial thickness exceeding 30 mm. Therefore, the success rate in our study was not affected by our criterion for endometrial thickness. We agree that endometrial thickness alone may not be a sensitive indicator of the need for vacuum aspiration, as demonstrated in our previous study.5 For the purpose of research, however, we had to set a cutoff point to standardize care within the study, thus permitting an objective estimate of efficacy.
Jun Zhang, Ph.D., M.D.
National Institute of Child Health and Human Development
Bethesda, MD 20892
zhangj@mail.nih.gov
Mitchell D. Creinin, M.D.
University of Pittsburgh
Pittsburgh, PA 15213
Kurt Barnhart, M.D., M.S.C.E.
University of Pennsylvania
Philadelphia, PA 19104
for the Management of Early Pregnancy Failure Trial Group
References
Center for Drug Evaluation and Research. FDA public health advisory: sepsis and medical abortion. Rockville, Md.: Food and Drug Administration, 2005. (Accessed November 1, 2005, at http://www.fda.gov/cder/drug/advisory/mifeprex.htm.)
Fischer M, Bhatnagar J, Guarner J, et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion. N Engl J Med 2005;353:2352-2360.
Hammill HA. Normal vaginal flora in relation to vaginitis. Obstet Gynecol Clin North Am 1989;16:329-336.
Miech RP. Pathophysiology of mifepristone-induced septic shock due to Clostridium sordellii. Ann Pharmacother 2005;39:1483-8.
Creinin MD, Harwood B, Guido RS, Fox MC, Zhang J, NICHD Management of Early Pregnancy Failure Trial Group. Endometrial thickness after misoprostol use for early pregnancy failure. Int J Gynaecol Obstet 2004;86:22-26.