Annexes

Annex 9: Clinical services domain PICO questions

PICO: P = population; I = intervention; C = comparator; O = outcome(s)[1] 

Pre-abortion

Rhisoimmunization

PICO 1: No anti-D administration in unsensitized Rh-negative individuals seeking abortion (see Recommendation 8 [NEW])

PICO question: For an unsensitized Rh-negative individual seeking abortion at < 12 weeks of gestation, is no administration of anti-D a safe and effective alternative to routine anti-D administration?

P: Unsensitized Rh-negative individuals seeking abortion at < 12 weeks (undergoing either medical or surgical abortion)

I: No anti-D administration

C: Routine anti-D administration

O:

  • Rate of isoimmunization in subsequent pregnancy
  • Rate of antibody formation after initial pregnancy.

Pain management for surgical abortion

PICO 2: Pain control for surgical abortion at < 14 weeks of gestation (see Recommendations 11 and 12 [NEW])

PICO question: For a pregnant person seeking surgical abortion at < 14 weeks of gestation, is pain control with any particular method (I) safer, more effective and/or more satisfactory/acceptable compared with pain control with a different method or no pain control (C)?

P: Pregnant persons seeking surgical abortion at less than 14 weeks of gestation.

I:

  • Paracervical block (PCB) [this includes the different concentrations, type (lidocaine), carbonated versus not, depth of injection]
  • PCB with premedication
  • Intravenous (IV) conscious sedation plus PCB
  • General anaesthesia
  • Topical anaesthesia (e.g. lidocaine)
  • Non-pharmacological intervention (music, acupuncture, “verbicaine”, etc.)

C:

  • No PCB
  • PCB alone
  • PCB with premedication
  • IV conscious sedation plus PCB

O:

  • Effectiveness (maximum pain as measured by visual analogue scale; VAS)
  • Anxiety scores using VAS
  • Safety (complications related to pain control methods, use of supplemental narcotic, use of any additional analgesic medication, duration of recovery time, hospital admission), side-effects
  • Satisfaction/acceptability.

PICO 3: Pain control for surgical abortion at ≥ 14 weeks of gestation (see Recommendations 11, 13 and 14 [NEW])

PICO question: For a pregnant person seeking surgical abortion at ≥ 14 weeks of gestation (including cervical priming prior to the procedure), is pain control with any particular method (I) safer, more effective and/or more satisfactory/acceptable compared with pain control with a different method or no pain control (C)?

P: Pregnant persons seeking surgical abortion at 14 weeks of gestation or above

I:

  • PCB [this includes the different concentrations, type (lidocaine), carbonated versus not, depth of injection]
  • PCB with premedication
  • IV conscious sedation plus PCB
  • General anaesthesia
  • Topical anaesthesia (e.g. lidocaine)
  • Non-pharmacological intervention (music, acupuncture, “verbicaine”, etc.)

C:

  • No PCB
  • PCB alone
  • PCB with premedication
  • IV conscious sedation plus PCB

O:

  • Effectiveness (maximum pain as measured by VAS)
  • Anxiety scores using VAS
  • Safety (complications related to pain-control methods, use of supplemental narcotic, use of any additional analgesic medication, duration of recovery time, hospital admission), side-effects
  • Satisfaction/acceptability.

Pain management for medical abortion

PICO 4: Pain control for medical abortion at < 14 weeks of gestation (see Recommendation 15)

PICO question: For a pregnant person seeking medical abortion at < 14 weeks of gestation, is pain control with any particular (i) pharmacological method (given prophylactically or after onset of pain) or (ii) non-pharmacological method safer, more effective and/or more satisfactory/acceptable compared with any other such method or no treatment/placebo?

P: Pregnant persons seeking medical abortion at < 14 weeks of gestation

I:

  1. Pharmacological methods [Timing: prophylactic or after onset of pain]
  • Ibuprofen
  • Acetaminophen plus codeine
  • Anti-emetics
  • Loperamide
  • Tramadol
  1. Non-pharmacological methods (music, acupuncture, “verbicaine”, etc.)

C:

  1. Pharmacological methods [Timing: prophylactic or after onset of pain]
  • Ibuprofen
  • Acetaminophen plus codeine
  • Anti-emetics
  • Loperamide
  • Tramadol
  1. Non-pharmacological methods (music, acupuncture, “verbicaine”, etc.)
  2. No treatment/placebo

O:

  • Effectiveness (maximum pain as measured by VAS)
  • Safety (complications related to pain-control methods, use of any supplemental narcotic, use of any additional analgesic medication), side-effects
  • Effectiveness of medical abortion regimen, defined as successful completion without additional surgical intervention
  • Time to expulsion
  • Satisfaction/acceptability.

PICO 5: Pain control for medical abortion at ≥ 14 weeks of gestation (see Recommendation 16 [NEW])

PICO question: For a pregnant person seeking medical abortion at ≥ 14 weeks of gestation, is pain control with any particular (i) pharmacological method (given prophylactically or after onset of pain) or (ii) non-pharmacological method safer, more effective and/or more satisfactory/acceptable compared with any other such methods or no treatment/placebo?

P: Pregnant persons seeking medical abortion at 14 weeks of gestation or above

I:

  • Pharmacological methods [Timing: prophylactic or after onset of pain]
  • Pretreatment (ibuprofen, acetaminophen plus codeine, antiemetics, loperamide, tramadol)
  • IV opiates
  • PCB
  1. Non-pharmacological methods (music, acupuncture, “verbicaine”, etc.)

C:

  1.  Pharmacological methods [Timing: prophylactic or after onset of pain]
  • Pretreatment (ibuprofen, acetaminophen plus codeine, antiemetics, loperamide, tramadol)
  • IV opiates
  • PCB
  1. Non-pharmacological methods (music, acupuncture, “verbicaine”, etc.)
  2. No treatment/placebo

O:

  • Effectiveness (maximum pain as measured by VAS)
  • Safety (complications, use of any supplemental narcotic, use of any additional analgesic medication), side-effects
  • Effectiveness of medical abortion regimen, defined as successful completion without additional surgical intervention
  • Time to expulsion
  • Satisfaction/acceptability.

Cervical priming

PICO 6a: Cervical priming at < 12 weeks of gestation (see Recommendation 17)

PICO question: For a pregnant person seeking surgical abortion at < 12 weeks of gestation, is cervical priming effective, safe and acceptable?

P: Pregnant persons seeking surgical abortion < 12 weeks

I: Cervical priming with medication or mechanical methods

C: Cervical priming with placebo, with medication (using different routes, doses or treatment intervals) or with different mechanical methods

O:

  • Effectiveness
  • Satisfaction/acceptability
  • Safety.

PICO 6b: Cervical priming at ≥ 12 weeks with medications (comparing different regimens) (see Recommendations 18b–d [NEW])

PICO question: For a pregnant person seeking surgical abortion at ≥ 12 weeks of gestation, is cervical priming with mifepristone plus misoprostol or with mifepristone alone a safe, effective and satisfactory/acceptable alternative to cervical preparation with misoprostol alone?

P: Pregnant persons seeking surgical abortion at ≥ 12 weeks

I: Cervical priming with

  • Mifepristone plus misoprostol [various routes, doses, intervals]
  • Mifepristone alone [various routes, doses, intervals]

C: Cervical priming with misoprostol alone [various routes, doses, intervals]

O:

  • Effectiveness (pre-procedure cervical dilatation, need for further dilatation, ease of procedure, time to complete procedure)
  • Safety (complications, need for additional interventions, pre- and post-procedure pain), side-effects
  • Satisfaction (client and provider)/acceptability
  • Cost (comparative cost and cost to the client).

PICO 7: Cervical priming at ≥ 12 weeks with medications compared with mechanical methods (see Recommendation 18b [NEW])

PICO question: For a pregnant person seeking surgical abortion at ≥ 12 weeks of gestation, is cervical priming with medical methods (mifepristone, misoprostol, or both) a safe, effective and satisfactory/acceptable alternative to mechanical methods (laminaria, foley bulb, dilapan)?

P: Pregnant persons seeking surgical abortion at ≥ 12 weeks

I: Cervical priming with medical methods

  • Mifepristone alone
  • Misoprostol plus mifepristone
  • Misoprostol alone

C: Cervical priming with mechanical methods (i.e. laminaria, foley bulb, dilapan)

O:

  • Effectiveness (pre-procedure cervical dilatation, need for further dilatation, ease of procedure, time to complete procedure)
  • Safety (complications, need for additional interventions, pre- and post-procedure pain), side-effects
  • Satisfaction (client and provider)/acceptability
  • Cost (comparative cost and cost to the client).

PICO 8: Cervical priming at ≥ 12 weeks with medication(s) plus laminaria compared with laminaria alone (see Recommendation 18d [NEW])

PICO question: For a pregnant person seeking surgical abortion at ≥ 12 weeks of gestation, is cervical priming with medication(s) plus laminaria a safe, effective and satisfactory/acceptable alternative to cervical preparation with laminaria alone?

P: Pregnant persons seeking surgical abortion at ≥ 12 weeks

I: Cervical priming with medication(s) plus laminaria

  • Mifepristone plus misoprostol plus laminaria
  • Misoprostol plus laminaria
  • Mifepristone plus laminaria

C: Cervical priming with laminaria alone

O:

  • Effectiveness (pre-procedure cervical dilatation, need for further dilatation, ease of procedure, time to complete procedure)
  • Safety (complications, need for additional interventions, pre- and post-procedure pain), side-effects
  • Satisfaction (client and provider)/acceptability
  • Cost (comparative cost and cost to the client).

PICO 9: Cervical priming at ≥ 12 weeks by mechanical method(s) before dilatation and evacuation (D&E) (see Recommendation 18 [NEW])

PICO question: For a pregnant person seeking surgical abortion (D&E) at ≥ 12 weeks of gestation, is cervical priming with one mechanical method a safe, effective and satisfactory/acceptable alternative to cervical priming with a different mechanical method?

P: Pregnant person seeking surgical abortion at ≥ 12 weeks

I: Cervical priming with one mechanical method before D&E

C: Cervical priming with a different mechanical method before D&E

O:

  • Effectiveness (pre-procedure cervical dilatation, need for further dilatation, ease of procedure, time to complete procedure)
  • Safety (complications, need for additional interventions, pre- and post-procedure pain), side-effects
  • Satisfaction (client and provider)/acceptability
  • Cost (comparative cost and cost to the client).

Abortion

New medical methods for abortion

PICO 10: Medical abortion with letrozole plus misoprostol, compared with misoprostol alone (see Recommendation 27c [NEW])

PICO question: For a pregnant person seeking medical abortion, is medical abortion with letrozole plus misoprostol a safe, effective and satisfactory/acceptable alternative to medical abortion with misoprostol alone?

P: Pregnant persons seeking medical abortion (all gestational ages)

I: Medical abortion with letrozole plus misoprostol [various routes, doses, intervals]

C: Medical abortion with misoprostol alone [various routes, doses, intervals]

O:

  • Effectiveness (ongoing pregnancy rate, procedure completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost (comparative and cost to the client).

PICO 11: Medical abortion with letrozole plus misoprostol, compared with mifepristone plus misoprostol

PICO question: For a pregnant person seeking medical abortion, is medical abortion with letrozole plus misoprostol a safe, effective and satisfactory alternative to medical abortion with mifepristone plus misoprostol?

P: Pregnant persons seeking medical abortion (all gestational ages)

I: Medical abortion with letrozole plus misoprostol [various routes, doses, intervals]

C: Medical abortion with mifepristone plus misoprostol [various routes, doses, intervals]

O:

  • Effectiveness (ongoing pregnancy rate, completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost (comparative and cost to the client).

PICO 12: Medical abortion with mifepristone plus letrozole, compared with misoprostol alone

PICO question: For a pregnant person seeking medical abortion, is medical abortion with mifepristone plus letrozole a safe, effective and satisfactory alternative to medical abortion with misoprostol alone?

P: Pregnant person seeking medical abortion

I: Medical abortion with mifepristone plus letrozole [various routes, doses, intervals]

C: Medical abortion with misoprostol alone [various routes, doses, intervals]

O:

  • Effectiveness (ongoing pregnancy rate, completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost (comparative and cost to the client).

Missed abortion at < 14 weeks of gestation

PICO 13: Medical management of missed abortion with mifepristone plus misoprostol (see Recommendation 31 [NEW])

PICO question: For a pregnant person with missed abortion at < 14 weeks of gestation, is medical management with mifepristone plus misoprostol a safe, effective and satisfactory/acceptable alternative to medical management with misoprostol alone?

P: Pregnant persons with missed abortion < 14 weeks

I: Medical management with mifepristone plus misoprostol [various routes, doses, intervals]

C: Medical management with misoprostol alone [routes, doses, intervals]

O:

  • Effectiveness (failed expulsion/ongoing retained products, completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost of treatment.

PICO 14: Medical management of missed abortion with all regimens (see Recommendation 31 [NEW])

PICO question: For a pregnant person with missed abortion at < 14 weeks of gestation, is medical management (all regimens) a safe, effective and satisfactory/acceptable alternative to expectant management?

P: Pregnant persons with missed abortion < 14 weeks

I: Medical management (all regimens)

C: Expectant management

O:

  • Effectiveness (failed expulsion/ongoing retained products, completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost of treatment.

PICO 15: Surgical management of missed abortion (see Recommendation 31 [NEW])

PICO question: For a pregnant person with missed abortion at < 14 weeks of gestation, is surgical management a safe, effective and satisfactory/acceptable alternative to medical or expectant management?

P: Pregnant persons with missed abortion < 14 weeks

I: Surgical management

C:

  • Medical management
  • Expectant management

O:

  • Effectiveness (failed expulsion/ongoing retained products, completed without surgical intervention
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Satisfaction/acceptability
  • Cost of treatment.

Self-management approaches

Self-management of medical abortion (see Recommendation 49)

PICO 16: Self-management of medical abortion

PICO question: For a pregnant person seeking medical abortion, is self-management of the process of medical abortion (assessing eligibility, administration of mifepristone and/or misoprostol, self-assessing outcome/success), without direct supervision of a trained health worker, a safe, effective and satisfactory/acceptable alternative to medical abortion managed by a trained health worker?

P: Pregnant persons seeking medical abortion at any gestational age

I: Pregnant persons self-managing the process of medical abortion (in whole) without direct supervision of a trained health worker

C: Medical abortion managed by a trained health worker (all medication abortion regimens)

O:

  • Effectiveness (success of abortion without need for surgical intervention following the procedure)
  • Safety (serious adverse events and complications)
  • Satisfaction/acceptability
  • Physical and emotional experience (side-effects, positive and negative emotions, internalized stigma), knowing when to seek medical care (unscheduled visits, phone calls to the clinic, emergency visits)
  • Cost.

PICO 16a: Self-assessment of eligibility for MA

PICO question: For a pregnant person seeking medical abortion, is self-assessment of eligibility[2] for medical abortion a safe, effective and satisfactory/acceptable alternative to eligibility assessment by a physician or other trained health-care provider?

P: Pregnant persons seeking medical abortion at any gestational age

I: Pregnant persons self-managing the first part of the medical abortion process by self-assessing their eligibility for medical abortion without direct supervision of a health-care provider

C: Eligibility assessment performed by a trained health-care provider

O:

  • Proportion of pregnant persons deemed eligible for medical abortion
    • Proportion of pregnant persons who were deemed ineligible due to gestational age
    • Proportion of pregnant persons who were deemed ineligible due to contraindications
  • Accuracy of these assessments when measured against an independent verifier and/or diagnostic standard
  • Ongoing pregnancy
  • Completed without surgical intervention
  • Safety (serious adverse events and complications)

PICO 16b: Self-administering medications for medical abortion

PICO question: For a person seeking medical abortion, is self-administration of medications for medical abortion, when provided with instructions for their use from a reliable source, a safe, effective and satisfactory/acceptable alternative to administration of medications by a trained health worker?

P: Pregnant persons seeking medical abortion at any gestational ages

I: Pregnant persons self-administering the medications for medical abortion (as part of the medical abortion process) without direct supervision by a health-care provider (but with instructions from a reliable source of health care)

C: Administration of medications for medical abortion by a trained health worker

O:

  • Pregnant persons’ adherence to the recommended medical abortion regimen following instructions
  • Effectiveness (ongoing pregnancy rate, completed without surgical intervention)
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment
  • Physical and emotional experience (side-effects, positive and negative emotions, internalized stigma), knowing when to seek medical care (unscheduled visits, phone calls to the clinics, emergency visits)
  • Satisfaction/acceptability
  • Cost (comparative and cost to the client).

PICO 16c: Self-assessment of the outcome of the medical abortion process

PICO question: For an individual who has undergone medical abortion, is self-assessment of the outcome/success of medical abortion a safe, effective and satisfactory/acceptable alternative to assessment of the outcome/success by a trained health worker?

P: Individuals who have undergone medical abortion

I: Pregnant persons self-managing the last part of the medical abortion process by self-assessing the outcome/success of the abortion without direct supervision by a trained health worker

C: Assessment of outcome/success of abortion by a trained health worker

O:

  • Effectiveness (proportion of pregnant persons assessed to have successful abortion, accuracy of these assessments when measured against an independent verifier and/or diagnostic standard)
  • Ongoing pregnancy rate
  • Completed without surgical intervention
  • Safety (serious adverse events and complications), side-effects
  • Expulsion time from initiation of treatment;
  • Physical and emotional experience (side-effects, positive and negative emotions, internalized stigma), knowing when to seek medical care (unscheduled visits; phone calls to the clinics, emergency visits)
  • Satisfaction/acceptability
  • Cost (comparative and cost to the client).

Footnotes

  1. For further information on the findings of the reviews based on the PICOs presented in this annex, refer to the EtD frameworks in Supplementary material 2.
  2. Eligibility criteria defined as: < 12 weeks; no contraindications; no signs or symptoms of ectopic pregnancy.