MIFEPRISTONE/MISOPROSTOL ABORTION: STEP BY STEP*

^{*Steps for telemedicine are the same as in-clinic care. Additional details for telemedicine are highlighted in italics. Also consider checking state-based regulations and/or consulting legal resources regarding telemedicine MAB.}

FIRST VISIT – DAY 1

Initial Counseling

• Introduce and build rapport with the patient
• Discuss pregnancy / abortion options (medication vs. aspiration) and patient concerns
• Reassure patient that abortion is safe, and does not interfere with future pregnancy if so desired.
• Telemedicine visit can be done via audio only or with video if available
  • Determine if eligible for telemedicine MAB and if patient desires using telemedicine
  • Consider disparities in access to electronic devices and reliable phone and internet service on the ability of patients to access care via telemedicine.

Patient Eligibility

• Determine pregnancy dating. MAB is appropriate for <77 days from anticipated day of mifepristone use (within 1 week of certainty) in addition to the following:
  • • Regular menses
    • First positive pregnancy test less than 6 weeks ago
    • No ectopic risk factors (previous ectopic, history of PID or tubal ligation, IUD in place at the time of conception, bleeding since LMP, or unilateral pelvic pain).
    • If LMP is unknown, a series of questions (Are you >10 weeks pregnant? Have you missed >2 periods? Are you >2 months pregnant?) may be used to determine eligibility for medication abortion (Ralph 2021).
  • If above criteria are not met and /or GA remains uncertain, US dating is recommended to confirm gestational age <77 days from anticipated day of mifepristone use. Some providers use a lower gestational age limit to allow for error when US is not used.

• Review medical history for absolute & relative contraindications to MAB:
  • IUD in place (must be removed prior to administration of the medications)
  • Allergy to a medication (eg mifepristone or misoprostol)
  • Chronic adrenal failure or long-term use of systemic corticosteroid therapy
  • Known or suspected ectopic pregnancy
  • Hemorrhagic disorders or concurrent anticoagulant therapy or symptomatic anemia
  • Inherited porphyria
  • No severe or unstable chronic condition that increases risk of outpatient procedure

• Telemedicine visit: Determine if eligible for telemedicine MAB. If a patient has sure LMP of <77 days and no history or symptoms concerning for ectopic pregnancy, they are eligible for telemedicine MAB without US. US can be used in cases where uncertainty exists to confirm pregnancy location and gestational age.

No labs required, unless

• Rh (D) testing standards are evolving: If < 12 weeks from LMP, may forego Rh testing and Rh-D IG for MAB (NAF May 2022; WHO 2022). (See Ch 5 Rh Isoimmunization)
• Hemoglobin or hematocrit: If recent history or symptoms of anemia. Rare for clinically significant drop in hemoglobin after MAB.
• Chlamydia/gonorrhea screen: If symptoms, risk factors, or by patient preference.
• For US requirements, see criteria listed above for patient eligibility.
• Telemedicine visit: same guidelines as above

Informed Consent

• Confirm confidential contact information.
• Discuss safety of MAB and review risks (see Complications Table):
  • Overall, early MAB is at least tenfold safer than continuing a pregnancy to term, although the magnitude of safety varies across global settings.
  • Additional misoprostol doses or aspiration with their risks, if indicated
  • Heavy or prolonged bleeding can occur in up to 3% of cases; Management options include misoprostol, NSAIDs, and non-urgent uterine aspiration. Rarely emergent uterine aspiration or transfusion indicated.
  • Endometritis (<1%) is uncommon. Atypical Clostridial infection is very rare.
  • There is no evidence-based regimen for mifepristone reversal. Not taking misoprostol after mifepristone may be associated with heavy bleeding (Grossman 2015, Creinin 2020).
  • Mifepristone is not associated with teratogenicity.
  • Advise patient about the potential teratogenicity of misoprostol (associated with increased congenital deformities, Mӧbius syndrome, and limb defects).
• In the U.S., patients must review and sign required consents and agreements:
  • Manufacturer’s Patient Agreement and Medication Guide: Danco (https://earlyabortionpill.com), or GenBioPro (https://genbiopro.com)
• Telemedicine visit: patients can electronically sign consent forms and the patient agreement through an electronic platform such as Docusign. Alternatively, the consents can be reviewed over the phone and the patient can sign the forms at the clinic in-person without an additional provider visit.

Counseling on Abortion Process

• Provide anticipatory guidance for the abortion process and medication side effects:
  • Ask if the patient wants to have a support person available.
  • Some patients may experience vaginal bleeding after mifepristone, and should be advised to continue to use misoprostol as directed.
  • Cramping/pain occurs in >90% of patients, varies in intensity, peaks after misoprostol dose, and is typically improved by NSAIDs and warm compress/heating pad.
  • Common side effects of misoprostol include: nausea, vomiting, diarrhea, low-grade fever, chills and myalgias, and usually resolve within 6 hours of use.
  • If mifepristone or misoprostol are vomited (or fall out) less than 30 minutes after use, consider repeat dosing. Antiemetic medications can be used ahead of misoprostol if the patient has significant pregnancy-related nausea.
  • Vaginal bleeding is usually heaviest within 4-6 hours after misoprostol, often heavier than normal menses and accompanied by the passage of large clots.
  • Average bleeding duration is 9 days (range 1-45 days). A clinically significant drop in hemoglobin is rare. Intermittent spotting may last for up to one month.
  • A heavy first menses is common following MAB.
  • Patients bleeding > two pads per hour for > two consecutive hours need to be evaluated in-person.

• Review use of medications:
  • Mifepristone:
    • Works by interrupting progesterone, the primary hormone that prepares the endometrium for implantation. This results in menstrual bleeding and disruption of the endometrium.
      • One 200 mg tablet is swallowed
  • Misoprostol:
    • Stimulates uterus to contract and expel the pregnancy
    • Describe options for misoprostol so patient can choose their optimal route for home administration:
      • Buccal: place four 200 mcg tablets between gum & cheek for 30 minutes; then swallow remaining fragments. Patients may place 24-48 hours after mifepristone.
      • Vaginal: place four 200 mcg tablets as high as possible in the vagina. Patients may place 0-72 hours after mifepristone.
      • Sublingual: place 2-4 200 mcg tablets under the tongue for 30 minutes. Swallow remaining fragments. Patients may place 24-48 hours after mifepristone.
    • If >63 days LMP, a second dose of 800 mcg misoprostol 4 hours after the first dose can be considered; and if >70 days LMP, a second dose is recommended.
• Can forgo Rho(D)-IG for MAB (See Chapter 3 or 5).

• Pain management
  • NSAIDs are mainstay: Ibuprofen 600-800 mg PO q6-8h or equivalent.
  • Adjunct therapies:
    • Heating pads or hot water bottles can help (Akin 2001).
    • Acetaminophen may be added, though evidence lacking.
    • Transcutaneous electrical nerve stimulation improves MAB pain (Goldman 2021) if accessible.
    • Tramadol (Dragoman 2021) and pregabalin (Friedlander 2018) studies show trending but not statistically significantly improved pain
    • Oxycodone was not found to be superior to NSAIDs in pain scores or duration (Colwill 2019). If given, 4-6 tablets are likely adequate.
  • Engage in a shared decision making with patients to discuss the pros and cons of pain control options and offer what is feasible and reasonable.
  • There is no difference in pain management strategies for individuals with opioid use disorder except that opioid prescriptions should be avoided, adjunct therapies should be maximized, and medication-assisted treatment should be continued as prescribed (Synder 2018).
• For antiemetics, may offer ondansetron, promethazine, or metoclopramide for patient comfort and medication absorption.
• Prophylactic antibiotics are not recommended (NAF 2022, WHO 2022, SFP 2014)
• Offer to discuss contraception, remaining aware that some patients prefer not to discuss at time of abortion (Brandi 2018). If interested, review options and timing for initiation. Reassure patients that abortion does not affect future fertility and that fertility may resume within a week of an abortion.
  • Implant: placement at time of mifepristone enhances patient satisfaction without increasing MAB failure rates (Raymond 2016).
  • IUD: placement at follow-up visit after confirming MAB completion; may have slightly increased risk of expulsion (Sääv 2012).
  • Sterilization: consents must be signed (30-180 days prior to procedure in the U.S. for patients with public insurance), refer and offer an acceptable bridge method.
  • Injection: may start at any time, may be provided IM in clinic or SQ for home use. Advise that injection at time of mifepristone is associated with a slightly increased rate of continuing pregnancy on the order of 1-3% (Raymond 2016).
  • Hormonal contraceptives: may start at any time (Tang 2002).
  • Barrier methods: as soon as the patient resumes intercourse.
  • Offer emergency contraception and dispense or prescribe for future use if desired.
• Home instructions: Discuss how to reach provider on call, especially if the patient has:
  • No bleeding within 24 hours of misoprostol (a repeat dose of misoprostol or an US if not initially performed may be indicated)
  • Soaked >2 maxi-pads for two or more consecutive hours or symptoms of hypovolemia
  • Unmanageable pain despite taking analgesics prescribed
  • Sustained fever >100.4° F or onset of fever >24 hours after misoprostol
  • Abdominal pain, weakness, nausea, vomiting or diarrhea > 24 hrs after misoprostol
  • Plans to go to a hospital or emergency department. Most patients’ concerns can be addressed with reassurance and anticipatory guidance. Many patients can wait to see you in the office rather than be referred to an ER. If ER is needed, facilitation may help improve the patient experience and reduce unnecessary interventions.

DISPENSING MIFEPRISTONE

• FDA Mifepristone REMS requires that a certified healthcare provider or pharmacy registered with the distributors dispenses the medication to patients. Other clinicians working directly with registered providers may also directly dispense.
  • Prescribers must certify with Danco or Gen Bio Pro and complete a prescriber agreement and account setup form
  • If a MAB visit occurs in person, the medications can be directly dispensed in the office, but the patient does not need to take the mifepristone in the office.
  • For telemedicine visits, the clinic can set up a medication delivery system.
  • In late 2021, the FDA removed the in-person dispensing requirement and added a requirement that pharmacies that dispense the medication be certified.
  • Please see Access Delivered Provider Toolkit for more information on setting up mail-order pharmacy distribution

^{(Source: Reproductive Health Access Project)}

FOLLOW-UP VISIT – DAY 7 – 14

1. Due to the safety and efficacy of MAB, studies demonstrate a range of follow up options are safe and reasonable. The chosen method should incorporate the preferences of the patient. Forgoing clinical follow up is likely safe, efficient, accessible, and acceptable, and some providers consider follow-up optional.
2. Follow up can be done by telemedicine or in-person visit. Review the patient’s course since taking medications, including timing and extent of bleeding and cramping, and resolution of pregnancy symptoms. Symptoms requiring an in-person evaluation:
   • No bleeding and cramping heavier than with a period
   • Continued heavy bleeding without improvement
   • Patient does not feel that the pregnancy has passed
   • Continued symptoms of pregnancy (nausea, breast tenderness)
   • Significant pain unrelieved by usual measures

3. Success of MAB can be assessed by a) clinical history and home urine pregnancy tests, b) by serial serum hCG testing, or c) by US.
   1. Clinical history (assessing symptoms by telemedicine or phone) is acceptable, when paired with a home urine pregnancy test after 5 weeks (Grossman 2011, Oppegaard 2015, Schmidt-Hansen 2019, Raymond 2021). Consider giving patient an additional pregnancy test so that they do not need to purchase one. Plan to call patient to confirm results of home pregnancy test 5 weeks post using medications
   2. When serial serum hCG protocol is used, a decrease from baseline hCG of 50% by 72 hours, 60% by 4-5 days (Pocious 2016), and 80% by 7 days from initiating treatment (Fiala 2003) is consistent with a successful MAB.
      • As serum hCG have physiologic decline in later first trimester, assess symptoms in conjunction with hCG if clinical suspicion for ongoing pregnancy.

4. When US is used, success is determined by demonstrating the absence of the previously identified pregnancy (gestational sac or embryo). Thickness of the endometrial stripe or presence of debris is not predictive of who will need intervention.
5. Review clinical course and results with patient. Have patient contact clinic for late-onset heavy bleeding or other concerns warranting evaluation and treatment.
6. Review contraceptive plan if desired.