HEALTH RISKS: MEDICAL ABORTION INFECTION
What Are The Risks?
Learn About Serious and Fatal Infections from Medical Abortion.
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What should a patient know about medical abortion infection complications?
Infection and hemorrhage are the most frequent serious and life-threatening causes of mifepristone related medical abortion illness and death. (3)
If pregnancy tissue or products of conception are retained in a patient’s uterus, the woman may have symptoms such as fever, chills, foul smelling discharge or bleeding and pain in the lower abdomen indicating a possible serious infection. (4)
Attention must be given to the possible outcome of infectious complications in medical termination of pregnancy. (5)
Infection may be suspected if a woman: (6)
- develops a fever of 38o C (100.4o F) or higher, that lasts for more than 4 hours, or a fever starts 6−8 hours after she has taken misoprostol
- has severe abdominal pain
- has pelvic tenderness.
Cases of reported of pelvic infections have been reported in recent literature when oral mifepristone was used with oral or vaginal misoprostol for medical abortion. (7)
There is no national system for tracking and reporting complications associated with gynecological procedures, the identification of true rates of reproductive tract infections in women is not readily available. (8)
FDA does not have sufficient information to recommend the use of prophylactic antibiotics for women having a medical abortion. Prophylactic antibiotic use carries its own risk of serious adverse events such as severe or fatal allergic reactions. (7)
How can incomplete abortion increase the risk of infection?
Incomplete medical abortion may increase the risk of infection and is associated with discomfort as persistent or recurrent bleeding and pain. (9)
Retention of blood clots and decidual fragments in case of incomplete abortion may increase the likelihood of septic events. (5) (10)
Incomplete abortion associated with excessive bleeding or infection is an indication for suction curettage. (11)
Any woman presenting with an incomplete abortion may also be experiencing one or more life-threatening complications: shock, severe vaginal bleeding, infection and sepsis. (12)
What should patients know about atypical infections and sepsis after medical abortion?
Serious bacterial infection after medical abortion can occur in the absence of the usual signs of typical pelvic infection. (13)
ATypical Presentation of Infection: Patients with serious bacterial infections (e.g. Clostridium sordellii) and sepsis (a serious infection involving the bloodstream) can present without fever, bacteremia or significant findings on pelvic examination following an abortion. Very rarely, deaths have been reported in patients who presented without fever, with or without abdominal pain, but with leukocytosis with a marked left shift, tachycardia, hemoconcentration, and general malaise. A high index of suspicion is needed to rule out serious infection and sepsis . (14) (see BOXED WARNINGS)
FDA recommends that healthcare professionals and patients be aware of the following: (15)
- All providers of medical abortion and emergency room health care providers should investigate the possibility of sepsis in patients who are undergoing medical abortion and present with:
- nausea, vomiting, or diarrhea and
- weakness with or without abdominal pain, and
- without fever or other signs of infection more than 24 hours after taking misoprostol.
- To help identify those patients with hidden infection, strong consideration should be given to obtaining a complete blood count.
The most commonly fatal adverse event is sepsis, which may progress rapidly to death. (3)
Since the approval of mifepristone (Mifeprex) in September 2000, the FDA has been informed of women who have died from serious infections following medical abortion with mifepristone and misoprostol. (1)
The FDA has concluded that patients who have died from serious infection involving the bloodstream after medical abortion may be possibly related to the use of mifepristone and misoprostol. (1)
The FDA has issued public health advisories to warn health care professionals about the risks of sepsis in medical abortion and to reinforce use of the approved regimen which does not include the vaginal use of misoprostol. (15) (16)
How can the alteration of vaginal Ph correlate with fatal Clostridium sordellii infection?
Bacteria vaginosis is the most common vaginal infection during the reproductive years. Vaginosis is characterized by vaginal pH values above 4.5 and is correlated with infections after induced abortions. (8)
Vaginal pH that correlates with pathogenicity results in the formation of bicarbonate/carbonic acid mixtures required for C. sordellii spore germination. (8)
The normal vaginal environment of a non-pregnant female lacks the necessary germination signals and is too acidic to allow C. sordellii spore germination. (8)
Altered vaginal pH conditions could result in a better environment for C. sordellii spores to germinate and establish infections. (8)
Blood, necrotic tissue and decreased pH enhance clostridial growth and exotoxin production. (17)
How can medical abortion drugs impair the innate immune response that may allow for serious or fatal infection?
As early as 1992, it has been suggested that the antiglucocorticoid effect of mifepristone would impair the immune system and favor the occurrence of infections. (18)
It has also been shown in rats that intrauterine misoprostol increases mortality from Clostridium sordellii infection by impairing or altering the immune response. (19)
Mifepristone and misoprostol both induce cervical dilation. Studies in rats show that cervical dilatation with mifepristone may allow for ascending infection of necrotic decidual tissue. (20) (21)
The opening of the cervical canal due to the antiprogestational effect of mifepristone may favor the migration of bacterial microorganisms that first colonizes the vagina/cervix then gaining access to the uterus. (10) (19)
In both medical and surgical abortions, vaginal bacteria enter the uterus via the open cervical canal but are removed by phagocytic cells of the innate immune system. (22)
To avoid the establishment of a myometrial infection during the recovery from the abortifacient process, the innate immune system must respond rapidly and appropriately to bacterial incursion of the decidua. (22)
Researchers, Jeanette I. Webster and Esther M. Sternberg have reported on the immune system response of the hypothalamic-pituitary-adrenal (HPA) axis on bacterial infections where interruption of the HPA axis by mifepristone (RU486) can enhance the severity or lethality of the infection. (23)
Interruption of the glucocorticoid response by the antiglucocorticoid (mifepristone) may play role in the pathological sequelae of exposure to a toxin (TcsL) produced by Clostridium sordellii. (24)
An important article by Ralph P Miech M.D. demonstrates the likely pathophysiologic basis for mifepristone’s capacity to increase a pregnant woman’s susceptibility to an otherwise rare cause of sepsis. (25)
The mechanisms of mifepristone action appears to favor the development of infection that leads to septic shock and intensifies the actions of multiple inflammatory cytokines, resulting in fulminant, lethal septic shock due to Clostridium sordellii. (25)
Mifepristone is long-lasting drug that can block steroid stress responses and the inflammation-dampening effects of cortisol. (26)
James A. McGregor M.D. and Ozlem Equiles M.D. suggest that mifepristone use impairs hosts responses and may predispose to lethal infection caused by toxigenic C. sordellii, other pathogens, and to reexamine the need for mifepristone use in medical termination of pregnancy. (17)
How are Clostridium sordelli infections associated with medical abortion?
The risk of severe, life-threatening, or even lethal adverse events, such as infection and sepsis, has been documented in otherwise healthy young women who have used mifepristone and misoprostol for medical abortion. (3) (7)
Clostridium sordellii is an emerging bacterial infection associated with toxic shock and has been associated with the medical abortion deaths in North America and Europe. (27) (28) (1) (29)
Since the approval of Mifeprex (Mifepristone, RU486) in September 2000 in the United States, the FDA has been informed of eight deaths in North America due to serious infections following medical abortion with mifepristone and misoprostol. These women died from sepsis (serious infection involving the bloodstream) and seven women were found to involve infection with bacterium, Clostridium sordellii and one case involved infection with Clostridium perfringens. (1) (27) (28) (30) (31)
In May of 2011, an additional death of a 16 year old Portuguese girl became the first fatality ever reported in the European community due to clostridium sordellii toxic-shock after medical abortion. (29)
Symptoms seen with clostridial infections include weakness, nausea, vomiting or diarrhea with or without abdominal pain that persists after expulsion of the pregnancy. Although patients typically lack a fever, they exhibit rapid pulse, low blood pressure, and very high red and white blood cell counts. (11) (14)
Clostridium sordellii is present in the vagina in 5% of all women and in up to 29% of women after pregnancy loss. (26)
Clostridium sordellii infections as a result of medically induced abortions have a 100% fatality rate. (32)
The risk of fatal sepsis in women is reported to be 10 times greater with medical abortion than surgical abortion (approximately 1 per 100,000 (7)). (33) (34)
Women who have died in the United States from sepsis (severe illness caused by infection of the bloodstream) after medical abortion with mifepristone and misoprostol: (7)
- Most of these women were infected with the same type of bacteria, known as Clostridium sordellii.
- The symptoms in these cases of infection were not the usual symptoms of sepsis.
Although medical termination is thought to be relatively safe, cases of significant infection combined with recently reported deaths highlights the need for enhanced vigilance for infection post medical termination of pregnancy. (13)
Patients, family planning providers, emergency medical personnel, infectious disease specialists and intensivists/hospitalists should all be made aware of the rare, but rapidly lethal, sepsis syndrome of Clostridium sordelli Associated Toxic Shock (CATS) subsequent to mifepristone (RU486) and misoprostol pregnancy termination. (35)
The FDA has concluded that serious or fatal infection involving the bloodstream after medical abortion may be possibly related to the use of mifepristone and misoprostol. (1)
The increased use of mifepristone/misoprostol to terminate early pregnancy may result in the increased risk of Clostridium sordellii infections in women. (8)
1. U.S. Department of Health & Human Services. Drugs, Mifeprex Questions and Answers, 2/24/2010. FDA, U.S. Food and Drug Administration. [Online] February 24, 2010. [Cited: July 16, 2011.] http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/ucm111328.htm.
2. Danco Laboratories, LLC. Health Professionals, Prescribing Information. Mifeprex, (Mifepristone) the early option pill to end pregnancy. [Online] 2011. [Cited: July 28, 2011.] http://www.earlyoptionpill.com/section/health_professionals/prescribing_information/.
3. Gary, Margaret M and Harrison, Donna J. Analysis of Severe Adverse Events Related to the Use of Mifepristone as an Abortifacient, Annals of Pharmacotherapy, 40(2): 191-7. NCBI, PubMed. [Online] February 2006. [Cited: September 13, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/16380436. PMID: 16380436.
4. IPAS India. Refresher course for medical abortion services, Reference manual, REFMA-IND-E09. IPAS. [Online] March 15, 2009. [Cited: January 17, 2011.] http://www.ipas.org/en/Resources/Ipas%20Publications/Refresher-course-for-medical-abortion-services-Reference-manual.aspx
5. Sitruk-Ware, Regine. Mifepristone and misoprostol sequential regimen side effects, complications and safety, Contraception 74 (1), 48-55. NCBI, PubMed. [Online] March 20, 2006. [Cited: September 12, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/16781261. PMID: 16781261.
6. International Consortium for Medical Abortion, ICMA Publications. The ICMA Information Package on Medical Abortion, Information for health care providers. International Consortium for Medical Abortion. [Online] 2011. [Cited: September 16, 2011.] http://www.medicalabortionconsortium.org/articles/for-health-care-providers/health/?bl=en.
7. U.S. Department of Health & Human Services. Drugs, Mifeprex (mifepristone) Information. FDA, U.S. Food and Drug Administration. [Online] July 19, 2011. [Cited: July 19, 2011.] http://www.fda.gov/drugs/drugsafety/postmarketdrugsafetyinformationforpatientsandproviders/ucm111323.htm.
8. Ramirez, Norma and Abel-Santos, Ernesto. Requirements for Germination of Clostridium sordellii Spores In Vitro, p. 418-425, Vol. 192, No. 2. Journal of Bacteriology. [Online] January 2010. [Cited: September 13, 2011.] http://jb.asm.org/cgi/content/abstract/192/2/418. doi:10.1128/JB.01226-09.
9. Rorbye, C, Norgaard, M and Nilas, L. Prediction of late failure after medical abortion from serial β‐hCG measurements and ultrasonography, European Society of Human Reproduction and Embryology, Volume 19, Issue1, Pp. 85-89. Oxford Journals, Human Reproduction. [Online] 2004. [Cited: September 8, 2011.] http://humrep.oxfordjournals.org/content/19/1/85.full. Online ISSN 1460-2350 – Print ISSN 0268-1161.
10. Sitruk-Ware, Regine and Spitz, Irving M. Pharmacological properties of mifepristone: toxicology and safety in animal and human studies, Contraception, 68(6): 409-20. NCBI, PubMed. [Online] June 17, 2003. [Cited: September 12, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/14698070. PMID: 14698070 .
11. National Abortion Federation. A Provider's Guide to Medical Abortion, Complications of Medical Abortion. National Abortion Federation, Early Options,. [Online] 2010. [Cited: August 2, 2011.] http://www.prochoice.org/education/cme/online_cme/m2complications.asp.
12. IPPF, Vekemans, Marcel. First trimester abortion guidelines and protocols. Surgical and medical procedures. International Planned Parenthood Federation. [Online] September 2008. [Cited: May 25, 2011.] www.ippf.org/system/files/abortion_guidelines_and_protocol_english.pdf
13. Lawton, Beverley, Rose, Sally B and Shepherd, Jill. Atypical presentation of serious pelvic inflammatory disease following mifepristone-induced medical abortion, Contraception 73 . NCBI, PubMed. [Online] April 2006. [Cited: September 14, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/16531180. PMID: 16531180.
14. U.S. Department of Health & Human Services. Drugs@FDA, Mifeprex (mifepristone) Label and Approval History. FDA, U.S. Food and Drug Administration. [Online] April 27, 2009. [Cited: July 12, 2011.] http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/020687s015lbl.pdf.
15. U.S. Department of Health & Human Services. Drugs, Public Health Advisory: Sepsis and Medical Abortion, November 4, 2005 Update. FDA, U.S. Food and Drug Administration. [Online] November 04, 2005. [Cited: July 16, 2011.] http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm051734.htm.
16. U.S. Department of Health & Human Services. Drugs, Public Health Advisory: Sepsis and medical abortion with mifepristone (Mifeprex). FDA, U.S. Food and Drug Administration. [Online] March 17, 2006. [Cited: July 13, 2011.] http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/DrugSafetyInformationforHeathcareProfessionals/PublicHealthAdvisories/ucm051298.htm.
17. McGregor, James A and Equiles, Ozlem. Risks of mifepristone abortion in context, Contraception, 72(5): 393; author reply 394. NCBI, PubMed. [Online] November 2005. [Cited: September 12, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/16246668. PMID: 16246668.
18. Brouckaert, P, Everaerdt, B and Fiers, W. The glucocorticoid antagonist RU38486 mimics interleukin-1 in its sensitization to the lethal and interleukin-6-inducing properties of tumor necrosis factor, Eur J Immunology, 22(4):981-6. NCBI, PubMed. [Online] April 22, 1992. [Cited: September 12, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/1532365. PMID: 1532365 .
19. Aronoff, David M, et al., et al. Misoprostol Impairs Female Reproductive Tract Innate Immunity against Clostridium sordellii. The Journal of Immunology, vol 180, no 12, 8222-8230. [Online] June 15, 2008. [Cited: July 25, 2011.] l. http://www.jimmunol.org/content/180/12/8222.abstract.
20. Van der Shoot, P. Treatment with mifepristone (RU486) and oestradiol facilitates the development of genital septic disease after copulation in female rats, Human Reproduction. [Online] May 1992. [Cited: September 13, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/1639975. PMID:1639975.
21. Spitz, Irving. Mifepristone: where do we come from and where are we going? Clinical development over a quarter of a century. Contraception, vol. 82, issue 5. November 2010, pp. 442-452.
22. Miech, Ralph P. Pathopharmacology of Excessive Hemorrhage in Mifepristone, Annals of Pharmacotherapy, Vol 41(12) 2002-7. NCBI, PubMed. [Online] December 2007. [Cited: September 12, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/17956963. PMID: 17956963.
23. Webster, Jeanette I and Sternberg, Esther M. Role of the hypothalamic–pituitary–adrenal axis, glucocorticoids and glucocorticoid receptors in toxic sequelae of exposure to bacterial and viral products, 181, p 207-221. Journal of Endocrinology. [Online] May 1, 2004. [Cited: September 5, 2011.] http://joe.endocrinology-journals.org/content/181/2/207.full.pdf+html.
24. Tait, Sasha A, et al., et al. The Large Clostridial Toxins from Clostridium sordellii and C. difficile Repress Glucocorticoid Receptor Activity, Infection & Immunity, 75(8): 3935-40. NCBI, PubMed. [Online] August 2007. [Cited: September 13, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/17517870. PMID: 17517870 .
25. Miech, Ralph P. Pathophysiology of Mifepristone-Induced Septic Shock Due to Clostridium sordellii, Annals of Pharmacotherapy, Vol 39(9). The Annals of Pharmacotherapy. [Online] September 2005. [Cited: September 12, 2011.] http://www.theannals.com/content/39/9/1483.abstract. doi: 10.1345/aph.1G189.
26. Worchester, Sharon. Mifepristone Deaths Raise Unanswered Questions, James A. McGregor, M.D. Ob.Gyn.News, Volume 40, Issue 19, page 13. [Online] October 2005. [Cited: June 28, 2011.] http://www.obgynnews.com/article/S0029-7437(05)71053-3/preview.
27. Cohen, Adam, et al., et al. Toxic Shock Associated With Clostridium sordellii and Clostridium perfringens After Medical and Spontaneous Abortion. Obstetrics & Gynecology, November 2007-Volume 110 -Issue 5 -pp 1027-1033. [Online] November 2007. [Cited: July 16, 2011.] http://journals.lww.com/greenjournal/fulltext/2007/11000/toxic_shock_associated_with_clostridium_sordellii.14.aspx.
28. Fischer, M, et al., et al. Fatal toxic shock syndrome associated with Clostridium sordellii after medical abortion, N Engl J Med;353:2352-60. New England Journal of Medicine. [Online] December 1, 2005. [Cited: July 20, 2011.] http://www.nejm.org/doi/pdf/10.1056/NEJMoa051620.
29. Reis, T, et al., et al. A Clostridium sordellii fatal toxic shock syndrome post-medical-abortion in Portugal, Abstract number: R2542. ESCMID, European Society of Clinincal Microbiolgy and Infectious Diseases, Milan, Italy. [Online] May 7-10, 2011. [Cited: September 12, 2011.] http://www.eccmidabstracts.com/abstract.asp?id=93762.
30. Sinave, Christian, et al., et al. Toxic Shock Syndrome Due to Clostridium sordellii: A Dramatic Postpartum and Postabortion Disease, Volume 35, Issue 11, pp. 1441-1443. Oxford Journals, Clinical Infectious Diseases. [Online] August 7, 2002. [Cited: September 12, 2011.] http://cid.oxfordjournals.org/content/35/11/1441.full?sid=a2610f54-ca62-403f-bce5-78e2eabb4bcf. doi: 10.1086/344464.
31. U.S. Department of Health & Human Services. Drugs, Postmarket Drug Safety Information for Patients and Providers, Related Information, Mifeprex Adverse Events Report as of April 2011. FDA, U.S. Food and Drug Administration. [Online] April 30, 2011. [Cited: July 19, 2011.] http://www.fda.gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsandProviders/UCM263353.pdf.
32. Aldape, M J, Bryant, A E and Stevens, D L. Clostridium sordellii Infection: Epidemiology, Clinical Findings, and Current Perspectives on Diagnosis and Treatment, Clinical Infectious Diseases, 43(11): 1436-1446. NCBI, PubMed. [Online] December 1, 2006. [Cited: September 13, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/17083018. PMID:17083018.
33. Greene, Michael F. Fatal Infections Associated with Mifepristone-Induced Abortion, N Engl J Med, 353(22):2317-8. NCBI, PubMed. [Online] December 1, 2005. [Cited: September 13, 2011.] http://www.ncbi.nlm.nih.gov/pubmed/16319378. PMID: 16319378.
34. Department of Health & Human Services, CDC, FDA, NIH. Emerging Clostridial Disease Workshop, May 11, 2006, James McGregor, pages 15-17. U.S. Department of Health & Human Services, U.S. Food and Drug Adminstration. [Online] June 22, 2006. [Cited: June 28, 2011.] http://www.fda.gov/downloads/AboutFDA/CentersOffices/CDER/UCM183030.pdf.
35. McGregor, James A and Equiles, Ozlem. Risks of mifepristone abortion in context, Response to letter to the editor. Contraception Journal. August, 2006, Vol. 74, 2, Pages 174-176.
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