Pregnant Participants, Fetuses, Neonates or In Vitro Fertilization

Overview
Inclusion of Pregnant People or People of Childbearing Potential
The Risk of Reproductive Harm and Contraception Requirements
Regulatory Requirements

Overview

Pregnant people, fetuses and neonates are categorized as vulnerable populations that require additional protections in the regulations (45 CFR 46 Subpart B) enforced by the Office for Human Research Protections (OHRP). These regulations also cover research using human in vitro fertilization, as well as human fetal tissue, placenta or post delivery fetal material.

UCSF supports a policy of providing pregnant people the same opportunities as non-pregnant people to participate in research, unless the individual meets legitimate exclusionary criteria or the study poses more than minimal risk to the fetus.

Inclusion of Pregnant People or People who can Become Pregnant

During the course of a clinical study, pregnant people or people who can become pregnant may be encountered coincidentally as potential participants. Alternatively, pregnant people and fetuses may be the target study population(s).

Some common types of research involving pregnant people include the following:

Pregnant people are not the target study population

If research targeting a wide population includes people who can become pregnant, there is the possibility of pregnancy. The research protocol should define any conditions for inclusion or exclusion of pregnant people or people who can become pregnant.

The consent form for treatment and interventional studies should describe any known risks to the participant (or to the embryo or fetus if the participant is or becomes pregnant). If the risks are not known because there is little experience in pregnant people, the consent form should clearly say so. See suggested consent form language below and in the consent form templates.

See the detailed IRB Requirements for additional conditions imposed by the regulations.

Pregnant people as the target study population

The IRB must consider the potential risks and benefits to the pregnant person and the fetus:

If the research holds the promise of directly benefiting the pregnant person or fetus, a greater than minimal risk to the fetus is acceptable.
If the research does not hold the prospect of directly benefiting the pregnant person or fetus, the research is allowed if the risk to the fetus is not greater than minimal.

Informed consent may be required from only the pregnant person or from the pregnant person and the other parent. Review the complete regulatory requirements below.

The Risk of Reproductive Harm and Contraception Requirements

Prospective study participants should be warned about possible reproductive or lactation risks from study treatments. Discuss these risks and the steps to be taken to minimize them in both the consent form and IRB Application.

The points that follow are adapted from a more specific discussion in the NIH Informed Consent Guidance for Human Gene Transfer Research: Reproductive Considerations, which also contains sample consent form language.

Discussions of reproductive harm

Include study-specific discussions of reproductive harm and measures taken to minimize harm. Factors to be considered include:

Direct teratogenic effects
Possible germline effects
Effects on the pregnant person’s ability to continue the current pregnancy
Effects on fertility and future pregnancies

In addition, reproductive harms and the steps to minimize them may depend on whether the participant can become pregnant, or whether they can cause a pregnancy. Address concerns appropriate to each participant population involved in the study.

Exclusion criteria and pregnancy testing requirements

Prospective participants in many studies should have the right to make a choice about the level of risk they will tolerate after having been fully informed of the study's risks and possible benefits.

However, if the study's risks justify the exclusion of pregnant or, nursing women or people who wish to start a pregnancy from a study, explain the reasons for the exclusion and the steps to be taken to avoid problems, such as pregnancy testing prior to treatment and periodically during the study.

Required methods of contraception

Methods of contraception required by the study should be adequate to address the study's specific risks. Clarify the time period when steps should be taken — before, during and/or after treatment.

Choices of methods should be as broad as is consistent with participant safety. Participants should be told the short- and long-term advantages and disadvantages of the allowable methods. Barrier methods should be used where body fluids may transfer infectious agents, vectors, or medications.

What if pregnancy occurs?

The application and consent documents should discuss what will happen if a study participant or the partner of a participant becomes pregnant. Typically, the participant should contact the investigator, who can then discuss risks and provide counseling about additional steps to be taken.

If the female participant is withdrawn from the study as a result of a pregnancy, the researcher may want to obtain information about the progress and outcome of a pregnancy for safety purposes. This information should be included in the consent form and may occur as long as the participant does not withdraw consent. Additionally, the investigator should submit a Protocol Violation/Incident Report via iRIS to the IRB if either the participant or the participant’s partner becomes pregnant.
If both the participant who becomes pregnant and the investigator wish to continue the participant’s enrollment in the study, a single subject modification (i.e., an enrollment exception) should be submitted to the IRB.

If the pregnant participant is withdrawn from the study as a result of a pregnancy, the researcher may want to obtain information about the progress and outcome of a pregnancy for safety purposes. This information should be included in the consent form and may occur as long as the participant does not withdraw consent. Additionally, the investigator should submit a Protocol Violation/Incident Report via iRIS to the IRB if either the participant or the participant’s partner becomes pregnant.
If both the participant who becomes pregnant and the investigator wish to continue the participant’s enrollment in the study, a single subject modification (i.e., an enrollment exception) should be submitted to the IRB.

Sample Consent Form Wording: The sample consent form wording that follows is adapted from the NIH Gene Transfer guidelines. The NIH guidelines include a number of additional examples that will be useful in many different kinds of studies. The wording in any example will need to be adapted to the particular study and participant population.

Examples

Example 1: You should not be in this study if you are pregnant or nursing or if you are planning a pregnancy soon. The [study treatments—Name the relevant treatments.] may cause harm to you and to unborn or breast-feeding children. You should not become pregnant during the study. If you can become pregnant or cause a pregnancy, you must use an adequate form of birth control. If you are able to become pregnant, you must have a negative pregnancy test within [time] before you get the first [treatment], and you will be tested for pregnancy every [interval] during the study. If you become pregnant while in this study, you should tell the study doctor immediately. The study doctor will counsel you about your choices.

Example 2: You should not exchange body fluids with another person after you start the [treatment] and for [time period] after the [treatment] stops. The best way to avoid exchanging fluids is to abstain from sexual activity for the [time period] you are in active treatment. Other, less effective ways to avoid exchanging fluids include barrier contraceptive methods such as [specify].

Regulatory Requirements

Definitions

As described in 45 CFR 46.202:

Dead fetus: A fetus that does not exhibit a heartbeat, spontaneous respiratory activity, spontaneous movement of voluntary muscles, or pulsation of the umbilical cord.

Delivery: Complete separation of the fetus from the pregnant person by expulsion or extraction or any other means.

Fetus: The product of conception from implantation until delivery.

Minimal risk: The probability and magnitude of harm or discomfort anticipated in the research are not greater in and of themselves than those ordinarily encountered in daily life or during the performance of routine physical or psychological examinations or tests.

Neonate: A newborn

Nonviable neonate: A neonate after delivery that, although living, is not viable

Pregnancy: Encompasses the period of time from implantation until delivery. A person shall be assumed to be pregnant if they exhibit any of the pertinent presumptive signs of pregnancy, such as missed menses, until the results of a pregnancy test are negative or until delivery.

Secretary: The Secretary of Health and Human Services and any other officer or employee of the Department of Health and Human Services to whom authority has been delegated.

Viable neonate: A neonate able, after delivery, to survive (given the benefit of available medical therapy) to the point of independently maintaining heartbeat and respiration.

Click on the link to expand the regulatory requirements for research involving each participant population.

Pregnant people or fetuses prior to delivery

45 CFR 46.204

All conditions must be met:	Informed consent requirements:
Where appropriate, prior animal studies and clinical studies with non-pregnant participants have been conducted and provide data for assessing potential risks to pregnant participants and fetuses..	The consent form clearly explains the reasonably foreseeable impact of the research on the pregnant participant and the fetus.
Any risk is the least possible for achieving the objectives of the research;	Consent will be obtained from the appropriate individuals as follows:
The risk to the fetus is caused solely by interventions or procedures that hold out the prospect of direct benefit for the participant or the fetus; or, If there is no such prospect of benefit, the risk to the fetus is not greater than minimal, and the purpose of the research is the development of important biomedical knowledge which cannot be obtained by any other means.	The pregnant participant or their legally authorized representative if: The research holds out the prospect of direct benefit to the pregnant participant, or, The research holds out the prospect of a direct benefit both to the pregnant participant and the fetus; or The research does not hold out the prospect of direct benefit for the participant or the fetus, but the risk to the fetus is not greater than minimal and the purpose of the research is the development of important biomedical knowledge that cannot be obtained by any other means.
No inducements, monetary or otherwise, will be offered to terminate a pregnancy.	The pregnant participant and the other parent if: The research holds out the prospect of a direct benefit solely to the fetus unless the other parent is unavailable, incompetent, or temporary incapacitated, or the pregnancy resulted from rape or incest. In cases where the other parent is not reasonably available, a statement to this effect must be signed by the pregnant participant.
Investigators will have no part in decisions about the timing, method, or procedures used to terminate a pregnancy or decisions regarding the viability of a fetus.	For minors who are pregnant, assent and permission are obtained in accord with the provisions of the Protections for Children Involved as Participants (Subpart D). For UCSF guidance on research involving minors, see the Children and Minors in Research page.

Neonates of uncertain viability

45 CFR 46.205

All conditions must be met:	Informed consent requirements:
Where appropriate, prior animal studies and clinical studies with non-pregnant participants have been conducted and provide data for assessing potential risks to pregnant participants and fetuses.	The consent form clearly explains the reasonably foreseeable impact of the research on the neonate.
Investigators engaged in the research will have no part in ending the pregnancy or in determining the viability of a neonate.	Informed consent is obtained from either parent of the neonate or, if neither parent is able to consent because of unavailability, incompetence, or temporary incapacity, consent is obtained from either parent's legally authorized representative. If the pregnancy resulted from rape or incest, consent does not need to be obtained from the person who caused the pregnancy or their legally authorized representative.
Until it has been ascertained whether or not a neonate is viable, a neonate may not be involved in research covered by this subpart unless the IRB determines that: The research holds out the prospect of enhancing the probability of survival of the neonate to the point of viability, and any risk is the least possible for achieving that objective, or The purpose of the research is the development of important biomedical knowledge which cannot be obtained by other means and there will be no added risk to the neonate resulting from the research

Nonviable neonates

45 CFR 46.205

All conditions must be met:	Informed consent requirements:
Vital functions of the neonate will not be artificially maintained;	The informed consent of both parents of the neonate will be obtained. However, if either parent is unable to consent because of unavailability, incompetence, or temporary incapacity, the informed consent of one parent will suffice. If the pregnancy resulted from rape or incest the consent of the person who caused the pregnancy is not needed.
The research will not terminate the heartbeat or respiration of the neonate;	The consent of a legally authorized representative of either or both of the parents of a nonviable neonate will not suffice.
There will be no added risk to the neonate resulting from the research;
The purpose of the research is the development of important biomedical knowledge that cannot be obtained by other means.

After delivery, the placenta, the dead fetus or fetal material

45 CFR 46.206

Research involving, after delivery, the placenta; the dead fetus; macerated fetal material; or cells, tissue, or organs excised from a dead fetus, shall be conducted only in accord with any applicable Federal, State, or local laws and regulations regarding such activities.

If identifying data are associated with the material in a manner that living individuals can be identified, directly or through identifiers linked to those individuals, those individuals are research subjects and all pertinent privacy protection measures are applicable.

Additional guidance on fetal tissue transplantation research is available on the OHRP website.

Research not otherwise approvable

45 CFR 46.207

The Secretary will conduct or fund research that the IRB does not believe meets the requirements of Sec. 46.204 or Sec. 46.205 only if:

The IRB finds that the research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant people, fetuses or neonates; AND

The Secretary, after consultation with a panel of experts in pertinent disciplines (for example: science, medicine, ethics, law) and following opportunity for public review and comment, including a public meeting announced in the Federal Register, has determined either:

That the research in fact satisfies the conditions of Sec. 46.204, as applicable; OR
The research presents a reasonable opportunity to further the understanding, prevention, or alleviation of a serious problem affecting the health or welfare of pregnant people, fetuses or neonates;
The research will be conducted in accord with sound ethical principles; AND
Informed consent will be obtained in accord with the informed consent provisions of Federal Policy for Protection of Human Subjects (Subpart A).

Research involving human in vitro fertilization

Although there is currently no federal funding of human in vitro fertilization (IVF) research, some UCSF investigators may be involved in privately-funded research on IVF as a treatment for infertility. The organizations shown below offer background information, historical perspectives on the regulatory issues and ethical guidance for IVF research:

Important Note: Research may require review by the Human Gamete, Embryo and Stem Cell Research (GESCR) Committee at UCSF.