Pregnancy Considerations for Research Protocols
When developing a research protocol, investigators should carefully consider whether pregnant participants may be enrolled, whether pregnancy should be an exclusion criterion, and when pregnancy testing is appropriate. This page provides practical guidance for protocol development and informed consent.
When developing a research protocol, investigators should carefully consider whether pregnant participants may be enrolled, whether pregnancy should be an exclusion criterion, and when pregnancy testing is appropriate. This page provides practical guidance for protocol development and informed consent.
Including or Excluding Pregnant Participants
If your study intentionally enrolls pregnant women, fetuses, or neonates, the protocol must include sufficient information for the IRB to determine that the requirements of 45 CFR 46 Subpart B are met.
If your study does not intentionally enroll pregnant participants, but participants could become pregnant during the study and you intend for them to remain enrolled, your protocol should explain why continued participation is appropriate and how participant safety will be protected.
If pregnancy is an exclusion criterion and you later wish to keep a participant in the study after they become pregnant, you must submit a modification to the IRB before continuing research activities involving that participant.
Justifying Exclusion of Pregnant Participants
Because research participation may benefit pregnant individuals, exclusion should be based on scientific or safety considerations rather than routine practice.
Your protocol should explain why pregnant participants are excluded. Appropriate justifications may include:
- The study does not meet the requirements for enrollment under Subpart B.
- The study intervention has known risks during pregnancy.
- The potential risks during pregnancy are unknown.
- Pregnancy could affect the scientific validity of the study.
If pregnant participants are excluded, the informed consent document should briefly describe any known, suspected, or unknown risks to a fetus or breastfeeding infant and explain the reason for exclusion when appropriate.
Who Should Be Considered Able to Become Pregnant?
For research purposes, pregnancy testing should be based on whether a participant could become pregnant, not simply on age or sex.
In general, pregnancy testing is not necessary for individuals who:
- Have completed menopause,
- Have undergone hysterectomy, bilateral salpingectomy, or bilateral oophorectomy, or
- Do not have, and could not have during the study, a partner capable of fathering children.
Investigators should be aware that:
- Tubal ligation is not considered surgical sterilization because pregnancy, while uncommon, can still occur.
- A partner's vasectomy does not eliminate the need for pregnancy testing, because vasectomy also has a small failure rate.
- Pregnancy testing should not be required for participants who cannot become pregnant unless there is a strong scientific justification.
Protocols may use a different definition if scientifically justified, but the rationale should be explained. In consent documents, use phrases such as "participants who could become pregnant" rather than "women of childbearing potential."
Pregnancy Testing
Pregnancy testing should be performed only when the results will influence study decisions, such as determining eligibility or whether study interventions may safely continue.
When developing your protocol, consider:
- The timing and frequency of testing
- Whether urine or serum testing is appropriate
- The reproductive risks associated with the study intervention
- Whether testing differs from standard clinical practice
Pregnancy tests performed after study interventions have ended should be scientifically justified, since the results generally will not change participant management.
Special Consideration for MRI Research
Although non-contrast MRI is generally considered a minimal-risk procedure, a pregnancy test is required before research MRI examinations to exclude pregnancy.
This requirement reflects current practice because the safety of higher magnetic field strengths during pregnancy has not been fully established, even though routine non-contrast MRI is often performed during clinical care when medically indicated.
Choosing the Appropriate Pregnancy Test
The choice of urine or serum pregnancy testing should be based on the study population and the potential risks associated with the research intervention.
Factors to consider include:
- The potential reproductive risks of the study intervention
- The likelihood of pregnancy in the study population
- Whether testing is performed at screening only or repeatedly during the study
- The possibility of false-positive or indeterminate results in some populations
Home pregnancy tests should not be used to determine study eligibility or whether participants may continue research interventions that could pose reproductive risks because they may be interpreted incorrectly.
Pregnancy testing should be performed using either:
- A CLIA-certified laboratory, or
- An FDA-approved point-of-care testing system.
If travel to NIH creates a burden, testing may be performed at an appropriate outside clinical facility.
Pregnancy Language in the Consent Form
If pregnancy is relevant to the study, the informed consent document should describe:
- Known, suspected, or unknown risks to a fetus or breastfeeding infant
- Pregnancy testing requirements
- Contraception requirements, if applicable
- Any circumstances under which pregnancy would require discontinuation of study interventions
Sample language is available in the NIH Consent Library.