Failure

OVERVIEW OF MEDICAL ABORTION FAILURE

When is medical abortion considered a failure?

Medical abortion is typically considered a failure when a surgical procedure is performed to complete the abortion for any reason, including incomplete abortion, continuing (viable) pregnancy, hemorrhage, or patient request. ^{(1) (2)}

Failure is a well-known complication of medical abortion. Medical abortion protocols emphasize the importance of counseling women about the risk of failure. ⁽³⁾

Medical abortion failure requiring a surgical procedure can include: ^{(1) (4) (5) (6)}

• Heavy Bleeding/Hemorrhage and Anemia (especially with ongoing blood loss) (See BLEEDING)
• Incomplete Abortion (unresponsive to drug treatment)
  • Persistent Gestational Sac (GS) without cardiac activity
  • Profuse Bleeding due to blood clots or pregnancy tissue fragments
• Continuing (ongoing) pregnancy/True drug and method failure
• Orthostatic hypotension (extreme drop in blood pressure)
• Patient unable to return to clinic; no access to emergency services
• Patient preference to complete the procedure because she is tired of persistent bleeding
• Provider choice or error interventions
• Medically necessary interventions or threats to patients’ health

Failures, defined as cases requiring surgical procedure for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increases with longer durations of pregnancy. ⁽⁶⁾

Women must be informed to return for a clinical examination in cases of acute or prolonged bleeding, pain or fever, as these signs may be indicators of failure or other complications that need treatment. ⁽⁷⁾

MEDICAL ABORTION FAILURE AT U.S. and FRENCH CLINICAL TRIALS

Clinical outcomes of the U.S and French studies following treatment with Mifepristone and Misoprostol which resulted in a surgical procedure due to medical abortion failure: ⁽⁶⁾

• Incomplete Abortion                           29-47 per 1000 women
• Continuing/Ongoing Pregnancy         10-13 per 1000 women
• Heavy Bleeding                                         3 per 1000 women
• Patient request                                          6 per 1000 women
• Medically necessary interventions           16 per 1000 women
• TOTAL FAILURE                                 45-79 per 1000 women

MEDICAL ABORTION FAILURE FROM 54 OTHER STUDIES

Outcomes of 54 studies following treatment with Mifepristone and Misoprostol which resulted in a surgical procedure due to medical abortion failure include: ^{(8) (9)}

• Incomplete Abortion
  • 20-40 per 1000 women at gestations up to 49 days
  • 50-80 per 1000 women at gestations of 50-56 days
• Continuing/Ongoing Pregnancy
  • 10-30 per 1000 women at gestations up to 49 days
  • 30-50 per 1000 women at gestations of 50-56 days
• Heavy Bleeding
  • 10 per 1000 women
• Retained Tissue & Persistent Bleeding
  • 10-20 per 1000 women
• Nonmedical indications
  • 10-20 per 1000 women

INCOMPLETE ABORTION

What happens if the procedure doesn't work?

The results of the U.S. and French clinical trials reported for incomplete abortion requiring surgical abortion after the administration of the FDA approved mifepristone and misoprostol regimen for pregnancy termination at less than 49 days gestation occurred in about 29-47 per 1000 women. ⁽⁶⁾

Alternative or off-label mifepristone regimens for pregnancies greater than 49 days gestation resulted in higher incomplete abortion rates.

Off-label/alternative mifepristone regimens have shown the use of oral misoprostol resulted in the risk of incomplete abortion in approximately 64 per 1000 women. ⁽⁴⁾

Off-label/alternative mifepristone regimens using vaginal misoprostol resulted in the risk of incomplete abortion in approximately 21 out of 1000 women. ⁽⁴⁾

Patients with incomplete abortions, defined as pregnancy termination with partial expulsion of the products of conception, were given the option of either waiting 1 week for the process to complete or having a vacuum aspiration. ⁽¹⁰⁾

Incomplete medical abortion may, however, increase the risk of infection (See WARNINGS) and is furthermore associated with discomfort as persistent or recurrent bleeding and pain. ⁽⁷⁾

Incomplete abortion associated with excessive bleeding or infection is an indication for suction curettage. ⁽⁴⁾

Any woman presenting with an incomplete abortion may also be experiencing one or more life-threatening complications: shock, severe vaginal bleeding, infection and sepsis. ⁽¹¹⁾ (See WARNINGS)

Persistent Gestational Sac (GS)

Due to the risk of incomplete abortion, all women should return to the clinic for a follow-up within 2 weeks after initiation of the medical abortion regimen to confirm pregnancy termination. ^{(4) (6)}

A woman with a persistent nonviable pregnancy can present with a gestational sac without signs of continued development or embryonic cardiac activity after an ultrasound procedure. ^{(4) (5)}

Guidelines vary and management of a persistent gestational sac (GS) can depend on several options for the woman: ^{(4) (5)}

• Option for a surgical abortion or uterine vacuum aspiration. ⁽⁴⁾
• The patient can be observed and re-evaluated after an additional 3-4 weeks for the sac to pass, prolonging the process. ⁽⁴⁾
• The patient may be administered a second dose of misoprostol where:
  • Less than half (50%) of women with a persistent GS will fail to expel their pregnancy. ⁽¹²⁾
  • Two-thirds (66%) of women who have a persistent GS with cardiac activity will fail to expel their pregnancy^{. (12)}
  • Increased age of women may be associated with higher failure rates. ⁽¹²⁾
  • Additional doses of misoprostol may not greatly improve the outcome. ⁽⁵⁾

CONTINUING PREGNANCY

What happens if the pregnancy continues?

Continuing pregnancy occurs when the medical abortion regimen fails to terminate the pregnancy. ⁽⁴⁾

Little to no bleeding 24 to 48 hours following misoprostol administration is cause for seeking follow-up care as it may be a sign of continued pregnancy. ⁽¹³⁾

A continuing pregnancy may result when the patient reports continued pregnancy symptoms and the provider finds the uterus is larger than on previous exam. ⁽¹³⁾

Patients with ongoing pregnancy (based on fetal cardiac activity or fetal growth consistent with a gestational age 2 weeks greater than at day 1 of starting the medical abortion regimen) are recommended to undergo vacuum aspirations. ⁽¹⁾

In the U.S. clinical trials, women presenting with embryonic activity 2 weeks after administration of mifepristone was not included in the definition of an incomplete abortion. This particular finding indicates a continuing pregnancy resulting in a failed medical abortion requiring a surgical termination. ⁽¹⁾

The U.S. and French clinical study reported continuing pregnancy using the FDA-approved medical abortion regimen in approximately 10 to 13 out of 1000 women. ⁽⁶⁾

A U.S. study of 2015 women in 1998 reported the failure rates of continuing pregnancy in women with gestations of up to nine weeks (63 days) duration: ⁽¹⁴⁾

• 10 per 1000 women had a continuing pregnancy at less than or equal to 49 days gestation
• 90 per 1000 women had a continuing pregnancy at 57 to 63 days gestation
• The mifepristone-misoprostol regimen for pregnancies more than 49 days gestation is less effective, with higher failure rates and a greater incidence of adverse events.

There is unsettled controversy about the respective efficacy and safety of 200 and 600 mg mifepristone in combination with misoprostol for the termination of pregnancy up to 63 days' gestation. ⁽¹⁵⁾

• Medical abortion regimens substituting 200 mg of mifepristone for the FDA approved 600 mg regimen may result in the risk of 1 % more continuing pregnancies. ⁽¹⁵⁾

The available evidence does not support routine substitution of 600 mg by 200 mg mifepristone for the medical termination of pregnancy when used with the approved dose of 400 mcg of oral misoprostol, unless the only relevant outcome is success and unless an excess rate of continuing pregnancies is considered to be only of secondary clinical relevance, which is questionable. ⁽¹⁵⁾

Possible Birth Defects if Pregnancy Continues

Congenital anomalies in continuing pregnancies that do not have a surgical abortion are a concern. (See WARNINGS) Patients must be certain of their decision to have an abortion and be willing to have a surgical abortion. ⁽²⁾

Women who choose to carry a pregnancy to term should be counseled on the possibility of birth defects and encouraged to seek active follow-up care throughout pregnancy. ⁽¹³⁾

Failure to Bleed & Continuing Pregnancy

Occasionally, a patient will experience little or no bleeding in the first 24 hours after the administration of the second drug, misoprostol. ⁽¹⁶⁾

Patients should seek prompt medical attention and evaluation where the lack of bleeding may be a possibly the result of: ⁽¹⁶⁾ (See WARNINGS)

• Undiagnosed ectopic pregnancy
• Continued pregnancy where surgical abortion will be necessary

The Role of Parity in Medical Abortion Failure ⁽¹⁷⁾

A 2008 research study of 1850 women in France intended to identify possible risk factors for failure of medical abortion with mifepristone and misoprostol.

Parity, which is the number of times a woman has given birth, may be a major factor influencing the success of medical abortion.

The study revealed that approximately 29 out of 1000 women experienced medical abortion failure requiring a surgical procedure.

The risk medical abortion failure when parity exceeds three has important implications for a patients’ counseling and may influence their choice of method, especially if a surgical method (vacuum aspiration) is more likely to be successful.