A Trial and Fertility Resource Guide

General Primary Prevention trial information, family planning considerations, fertility preservation and reproductive options for people at-risk of DIAD.

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Overview and General Information on the DIAN-TU Primary Prevention Trial

What is the Dominantly Inherited Alzheimer Network Trials Unit (DIAN-TU) Primary Prevention Trial? 
The Primary Prevention Trial is a DIAN-TU clinical trial that will begin in late 2024. This trial is open for people who are at risk for dominantly inherited Alzheimer’s disease (DIAD) and are 11 to 25 years away from their parent’s age of symptom onset. By treating as early as possible, this trial will test if it is possible to prevent DIAD and/or the pathology of the disease. 

What does Primary Prevention mean?
Primary prevention involves testing if it is possible to prevent disease (or disease pathology). Previous DIAN-TU trials have involved secondary prevention, which means the disease or pathology is present but treated early. 

What is the goal of the Primary Prevention Trial? 
The Primary Prevention Trial aims to prevent or slow down the formation of amyloid plaques (harmful protein clumps in the brain and the main pathology of Alzheimer’s) with the investigational drug remternetug. The hope is that by preventing amyloid plaques, the drug will also possibly prevent or substantially slow DIAD. 

Who can join the Primary Prevention Trial? 
You can join the trial if:

• You are 18 or older.
• You are 11 to 25 years younger than the age when your parent started showing symptoms of Alzheimer’s disease.
• You agree to learn your genetic status (whether you have a DIAD mutation) later in the trial.
• You are not pregnant, planning to become pregnant during the trial, or currently breastfeeding. 

How long do I have to decide if I want to join the trial? 
Enrollment, or the ability to join, the Primary Prevention Trial begins in November 2024. While enrollment for the trial depends on how fast or slow people join the trial, the DIAN-TU expects it will take take approximately 2-3 years.  

What if I am interested in joining the Primary Prevention Trial? 
If you are interested in enrolling in the Primary Prevention Trial, you can reach out to the DIAN Expanded Registry at dianexr@wustl.edu to learn about the trial. They will connect you with the DIAN-TU trial coordinator and a study site to ask questions about the trial and sign consent forms to join the trial.

How does the trial work? 
The Primary Prevention Trial has two parts or Stages.   

• Stage 1: Double-Blind Drug Trial (2024–2030)
  During this Stage of the trial, participants are randomly assigned to take either the active study drug (remternetug) or a placebo (a harmless substance). Neither the participants nor the researchers will know who is receiving the active study drug. Participants will receive a subcutaneous (under the skin) injection every 12 weeks. These can be done at a study site or a remote location of choice, such as your home or office. Participants will also travel to their study site approximately once a year for tests, including bloodwork and brain imaging (such as MRI scans), to track how the drug is working.  

• Stage 2: Open-Label Extension (2030–2034)
  During Stage 2, all participants will receive the active study drug, regardless of whether they were originally given the active study drug or the placebo. Because all participants will be receiving the active study drug during Stage 2, participants will be required to learn their genetic status. The DIAN-TU team will help coordinate genetic counseling. Study visits and frequency of injections will follow the same schedule as in Stage 1.

If I don’t know my genetic status, when will I need to undergo genetic testing? 
Genetic counseling and testing will be available at any time during Stage 1 but will have to be completed if participants would like to participate in Stage 2 of the trial. Thus, to get into Stage 2 of the trial, participants must learn their genetic status. 

How long do I need to stay in the trial? 
At the beginning of the Primary Prevention Trial, participants agree to participate in both Stage 1 and Stage 2 of the trial. A trial participant can decide to leave the trial at any time, but it is important for trial participants to enroll in the trial with the intention of staying in the trial until it is complete. 

What should I consider before enrolling in the trial? 
Participation in clinical research is completely voluntary. Clinical trials offer an opportunity for people at risk of developing DIAD to access potential disease-modifying treatments, as well as expand knowledge and research on Alzheimer’s disease therapies. However, clinical trials are not without some risks. Thus, it is important for participants to carefully weigh the benefits and risks of their own trial participation. 

• Access to New Treatments: You might receive a cutting-edge drug that could slow or prevent Alzheimer’s symptoms.
• Contribute to Science: Your participation will help researchers develop better treatments for Alzheimer’s.
• Hope for the Future: By joining, you’re supporting efforts to help future generations avoid this disease.
• Placebo Assignment: You might not get the active study drug during Stage 1.
• Drug Side Effects: The drug could cause unexpected health issues.
• Time Commitment: You’ll need to attend regular visits and tests, which involve time and travel.
• Emotional Impact: Learning your genetic risk could be stressful. You might also struggle with confronting the disease in a real way during dosing or study visits. 
• Physical discomfort: Some of the testing procedures may be uncomfortable (such as lumbar puncture, laying still in an MRI machine or blood draw). 
• Pregnancy Restrictions: You cannot get pregnant during the trial. If you are in your prime reproductive years, you may not want to put off having a family. 

Are there any resources for mental health and emotional support as I make a decision to join the trial? 
The trial team understands that participating can be emotionally challenging. DIAN-TU is developing a Mental Health Initiative to connect participants with counselors who specialize in DIAD-related issues. Upon request, the DIAN-TU can provide financial support to cover counseling sessions for each participant. The number of sessions will be reviewed with participants but may be up to 6–10.

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Fertility Resource Guide

This Fertility Guide offers information for individuals with a family history of dominantly inherited Alzheimer’s disease to make informed reproductive and family planning decisions. Given that the Primary Prevention Trial does not allow participants to become pregnant during the study, this guide aims to support participants in evaluating their family planning goals while deciding whether to join the trial.

The Fertility Guide is divided into three parts:

• Part 1: Family planning considerations for Primary Prevention Trial participation
  Fertility and family planning considerations that may help you make an informed decision about enrolling in the Primary Prevention Trial. You may find this guide to be a helpful place to start if you are interested in having a child in the next four to eight years.
• Part 2: Fertility preservation options for Primary Prevention Trial participants
  Since pregnancy is not allowed during the Primary Prevention Trial, some participants may need to choose between delaying family planning to join the trial or having a child and missing out on potential treatment. This guide can help you explore fertility preservation options to support your future family planning goals while participating in the trial.
• Part 3: Reproductive options for people at-risk of genetic diseases
  This part of the guide is useful for learning about reproductive options, especially for those in the DIAD community who are at risk of inheriting a disease-causing mutation and want to explore ways to avoid passing it on to their children.

Developments in science have opened many possibilities for individuals and couples who experience infertility to have biological children. This Fertility Guide acknowledges and respects all attitudes that vary among religious and cultural groups towards the use of assisted reproductive technologies. It is the aim of this Fertility Guide to present all available options to study participants and families so that they may make the most fully informed decisions about their future. In doing so, we present options that may conflict with an individual’s personal, religious, or cultural beliefs. Regardless of an individual’s and couple’s choice, we recommend that anyone who is at-risk for dominantly inherited Alzheimer’s disease and is interested in understanding their reproductive options, should seek out genetic and reproductive counseling.

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Fertility Guide Part 1: Family planning considerations for Primary Prevention Trial participation

If I am pregnant or plan to become pregnant soon, can I participate in Primary Prevention Trial? 
Unfortunately, no. DIAN-TU aims to be inclusive of everyone in its clinical trials, regardless of sex, race, ethnicity, socioeconomic status, or stage of life. However, because pregnancy can complicate research, individuals who are pregnant or plan to become pregnant during the study cannot participate in the Primary Prevention Trial. Additionally, participants who are currently breastfeeding are not eligible until they have finished breastfeeding.

Why is pregnancy not allowed during the trial?
Pregnancy is restricted for the following reasons:

• Safety concerns for fetus: The drug being tested, remternetug, has not been studied in pregnant people. While it may help slow or stop Alzheimer’s, it’s not known if the drug could harm a baby’s development. 
• Impact on memory: Pregnancy can cause temporary changes to a person’s memory and thinking¹. Since the trial tests brain function, these changes could interfere with researchers being able to detect how the drug influences memory. 
• Drug effectiveness: Pregnancy causes many changes in the body, including how the body processes medications. This could impact how well the drug works and make it harder for researchers to study its impact. 

What are the risks of getting pregnant while taking an investigational drug?  
It’s hard to know the exact risks of getting pregnant while taking an investigational drug. A study on Alzheimer’s disease in mice found no reproductive or developmental risks with an amyloid-targeting drug². However, this hasn’t been studied in humans, so we don’t know if the investigational drug in the trial could harm a pregnancy. 

How should I avoid becoming pregnant during the trial?
All women of reproductive age or people who can become pregnant (i.e., with a uterus) must use a reliable method of contraception (e.g., abstinence, IUD, or birth control) during their participation in the Primary Prevention Trial. 

What happens if someone becomes pregnant during the trial?
If a woman in the study becomes pregnant, she will need to stop taking the active study drug or placebo immediately. The study team will monitor the pregnancy and the baby at birth. For male participants, if their female partner becomes pregnant during the study, they will need to report the pregnancy to the study team so the baby can be monitored.

What if I change my mind? Can I leave the trial to have a child? 
Yes, a person can discontinue their study participation at any time. We would encourage potential participants to carefully weigh this decision before enrollment. Every DIAN-TU trial involves a tremendous amount of coordination and resources. The data and scientific knowledge gained from these trials is critical to our understanding of Alzheimer’s disease and identifying drugs that can delay the disease. Each participant and year of trial participation are important and make critical contributions to research. Leaving the trial prematurely would create gaps in the study. 

It is possible that at the end of the Double-Blind Drug Trial period an individual could get pregnant and then re-enter the Open Label Extension period after childbirth. The site study team and DIAN-TU leadership will consider this on a case-by-case basis. 

How long do I need to wait after the trial to get pregnant?
After a participant receives the last dose of drug in a clinical trial, there is a washout period to allow the drug to clear the body. For remternetug, this period is 20 weeks, so participants must wait at least 20 weeks before trying to become pregnant. 

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Fertility Guide Part 2: Fertility preservation options for Primary Prevention Trial participants

The Primary Prevention trial may last up to 10 years, which could affect family planning for people in their 20s, 30s, or 40s. If you want to have biological children, you might consider fertility preservation before joining the trial. This means saving eggs, sperm, or embryos for use after the trial ends.

How might participating in the trial affect my fertility and ability to conceive in the future? 
Age is a key factor in a person’s ability to become pregnant. For example, a 30-year-old woman has about a 20% chance of getting pregnant each month, but this chance drops over time. By age 35, that same woman has a 10% chance per month of getting pregnant, and by age 40, less than 5% chance³. So, delaying family planning for four to eight years during these important reproductive years could make it more challenging to conceive naturally.

I’m worried about losing important child-bearing years during my Primary Prevention Trial participation. What can I do?
Participants on medications or treatments for long periods during their reproductive years may face challenges later when trying to conceive naturally. A fertility consultation before joining the trial can help you understand the best options based on your age, timeline, and health. Fertility specialists can offer consultations, counseling, basic fertility testing, and follow-up appointments to discuss and explore fertility preservation options if needed.

What is fertility preservation? 
Fertility preservation is the process of saving eggs, sperm, or other reproductive tissue for future use in having biological children. Preserving fertility before joining the trial can give participants peace of mind, allowing them the option to have biological children or expand their family later, even if they are older at the end of the trial. 

If I am interested in preserving my fertility, what are my options? 

Option 1: Egg freezing: This process involves taking injectable hormones for about two weeks to help develop multiple mature eggs. Once matured, the eggs are collected through a simple outpatient procedure called egg retrieval. These eggs are then frozen and stored for future use.

• Time: Two to four weeks of hormone therapy
• Cost: $8,000–$20,000 USD (cost varies by location, clinic, number of cycles, and insurance)

Option 2: Embryo freezing: This process is similar to egg freezing, but after the eggs are retrieved, they are combined with sperm from a partner (or donor) to create embryos. These embryos are then frozen and stored for future use.

• Time: Two to four weeks of hormone therapy plus one week for fertilization and embryo growth
• Cost: $17,000–$33,000 USD (cost varies by location, clinic, number of cycles, number of embryos for genetic testing, type of genetic testing and insurance)

The cost of these procedures is expensive but in many states egg/embryo freezing and IVF are covered by insurance if it’s medically indicated/needed. Please contact Youngtimers.org or Resolve.org to learn more. 

If I freeze my eggs or embryos, do I have to use in-vitro fertilization to have a biological child?
Many women who freeze their eggs or embryos use in-vitro fertilization (IVF) to have a biological child. However, not all women who freeze their eggs will use them, and freezing eggs does not prevent natural conception. Many women can still conceive naturally after freezing their eggs or embryos. They may return to frozen eggs or embryos if they face infertility or want to expand their family later in life when pregnancy can become more challenging.

Can my eggs or embryos be tested for a DIAD mutation to avoid passing the disease to my child? 
Yes, embryos can be tested for a DIAD mutation, but eggs (or sperm) cannot be tested. IVF with preimplantation genetic testing (IVF-PGT) allows people who are at risk of a genetic disorder, like DIAD, to have a child without passing on the disease. Egg and embryo freezing are the first steps of the IVF-PGT process, so those who choose egg or embryo freezing are already in a good position to pursue IVF-PGT. After testing, only embryos that do not carry the mutation are implanted, ensuring the child won’t develop the disease. The cost of PGT (or genetically testing of embryos) is approximately $6,000-$10,000 USD, but costs vary depending on location, clinic, family situation, ease of probe development, and number of embryos tested.

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Fertility Guide Part 3: Reproductive options for people at-risk of genetic diseases

What family planning or reproductive options are available for people who are at-risk or carriers of a DIAD mutation? 

Options	Natural pregnancy	Natural pregnancy with prenatal testing**	IVF with preimplantation genetic testing (PGT)	Surrogate or gestational carrier	Egg or sperm donation	Adoption	Child-free
Description	Natural conception and birth	Genetic testing of fetus at 11-22 weeks of gestation	Implanting embryos that have been screened and do not have a DIAD mutation	Another person carries your baby  (will need to create embryos through IVF)	Use donor egg or sperm in place of DIAD partner	Raise a non-biological child	Choosing not to have a child
Risk of passing on disease	50%	No risk, if using selective termination.	Very low risk (<1%)	Dependent on method***	–	–	–
Risk of finding out personal genetic status	–	High risk	Low risk if choose non-disclosure PGT	–	–	–	–
Time*	–	Varies by genetic status and number of times it takes to become pregnant with a fetus that doesn’t carry the mutation.	Months – Years (based on cycles needed)	Time to find person	Dependent on method (IUI or IVF) ****	Months – Years	–
Cost*	$	$ (could be covered by insurance)	$$-$$$	$-$$$$	$$-$$$  (egg) $-$$ (sperm)****	$$-$$$	–
Other considerations	–	Invasive genetic testing is associated with a <1% of miscarriage.  Selective termination if a mutation is found may be difficult (termination laws vary by state in the US).	May need to involve family member for DNA sample.	Option if in trial***	–	–	–

* There are many factors that influence the time and cost of different reproductive and family planning options. The listed numbers in this table are estimates collected from various reputable sources. However, it is advised that each person investigate these numbers based on their own situation.

** In many cases, a commitment must be made by the couple (prior to the procedure) that they will agree to terminate the pregnancy if a mutation is found. Problems arise from finding the genetic status of an unborn child, who has no autonomy over this private health information. 

*** Surrogacy or gestationally carrying a child can be achieved multiple ways. If a person at-risk or a carrier of a DIAD mutation, wants to avoid passing on a mutation to their child, then they can create an embryo, perform genetic testing on the embryo, and transfer the embryo that has tested negative (IVF with PGT) into a surrogate or gestational carrier. If IVF with PGT is done, then the risk of passing on the disease is similar to IVF with PGT. If the donor egg or sperm are from a person at-risk or a carrier of a DIAD mutation and IVF with PGT isn’t done, then the risk of passing on the disease is the same as a natural pregnancy. 

**** Depending on the type of donation that Is needed, the time and cost of this option will be variable. An IUI, or intrauterine insemination, costs $300-$1,000, which would be done if using donor sperm (and fertility was not an issue). An IVF cycle costs $12,000-$24,000, which would be done if using donor eggs. 

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Additional Resources

DIAN-TU. To learn more about the trial visit: https://dian.wustl.edu/clinical-trials/primary-prevention-trial or contact the DIAN Expanded Registry via email at dianexr@wustl.edu, by phone at 1-844-342-6397 or by registering at https://dian.wustl.edu/items/exr-registry.

Youngtimers. To learn more about fertility and reproductive options and/or connect with others in the community who have undergone some of these options, visit www.youngtimers.org or email lindsay@youngtimer.org.

The American Society for Reproductive Medicine. A good resource to learn about IVF-PGT and other fertility procedures, explore insurance mandates in your state, and find a qualified health professional. Visit www.asrm.org. 

The Society for Assisted Reproductive Technology. A good resource to research the success of specific fertility clinics. Visit www.sart.org.

FertilityIQ. A website with easy-to-follow classes and videos on all things fertility. They also post reviews of fertility doctors. Visit www.fertilityiq.com. Contact lindsay@youngtimers.org for a code that gives free access to courses (generously given to all people at risk of DIAD ). 

Resolve. A great organization and site to learn about covering the financial costs of fertility options. It also organizes fertility support groups. Visit www.resolve.org. 

References

Prepared by: 
This Fertility Guide was prepared by Dr. Lindsay Hohsfield, PhD, a participant advisory group (young adults at-risk of DIAD and eligible for the Primary Prevention Trial – encompassing different perspectives, backgrounds, etc.), and the DIAN-TU leadership team. The participant advisory group identified critical questions/topics to be addressed in this Guide, provided feedback on content and reviewed materials. Dr. Hohsfield consulted fertility experts and literature to address these questions and topics. The accuracy of this information was reviewed and confirmed by DIAN-TU leadership, Katie Neimeyer, MS, CGC, a genetic counselor and Dr. Laxmi Kondapalli, MD, a board-certified reproductive endocrinologist and infertility specialist. 

Citations:

1. Barda, G. et al. The effect of pregnancy on maternal cognition. Scientific reports 11, 12187, doi:10.1038/s41598-021-91504-9 (2021). ↩︎
2. Barrow, P. et al. Reproductive and developmental toxicology studies with gantenerumab in PS2APP transgenic mice. Reproductive toxicology (Elmsford, N.Y.) 73, 362-371, doi:10.1016/j.reprotox.2017.07.014 (2017). ↩︎
3. Medicine, A. S. f. R. Age and Fertility, A Guide for patients. (2012). ↩︎

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Glossary

Amyloid plaques:  Amyloid plaques are one of the major hallmarks of a brain affected by Alzheimer’s disease. Amyloid plaques are made of amyloid-beta (or Aβ), which are short proteins that stick or clump together to form a cloud/ball-like structure in the brain. Research has shown that these plaques begin to form years before symptoms of Alzheimer’s are apparent, making them attractive targets for Alzheimer’s disease therapies.

Consent: To give permission for something to happen or be performed. In clinical trial research, investigators must provide adequate information (often provided in consent forms) that allows participants to make informed decisions about (and give consent for) their participation in a clinical trial. 

Cycles: IVF includes several steps: ovarian stimulation, egg retrieval, sperm retrieval, fertilization, and embryo transfer. One full cycle of IVF involves all of these steps and can take several weeks to months.   

Developmental or reproductive hazards: Reproductive hazards are substances that may affect or harm a person’s reproductive health or fertility. An example of a reproductive hazard is radiation, which may affect or reduce a person’s number of eggs or sperm if given at high doses. Developmental hazards are substances that may affect the healthy development of an embryo. An example of a developmental hazard is thalidomide, which causes abnormal limb development if given during pregnancy. 

Dominantly Inherited Alzheimer’s disease (DIAD): (also referred to as autosomal dominant Alzheimer’s disease, familial Alzheimer’s disease, or early-onset familial Alzheimer’s disease). A rare hereditary form of Alzheimer’s disease caused by known genetic mutations in APP, PSEN1 or PSEN2. Due to the hereditary nature (i.e., autosomal dominant inheritance pattern) of this disease, a parent who has a genetic mutation for DIAD has a 99.9% chance of being affected by the disease and a 50% chance of passing it on to a child.

Embryos: An embryo is created after fertilization of an egg cell with a sperm cell. For humans, embryos refer to unborn offspring between the second and eighth week after fertilization (after which it is called a fetus). 

Family planning: The ability of individuals and/or couples to plan and attain their desired number of children (including the spacing and timing of their births, as well as the choice to not have children). 

Fertility: The ability to conceive or have biological children. 

Genetic status: Awareness of certain genetic information. A person can undergo genetic testing to learn about their genetic status. In DIAD, some individuals decide to learn their genetic status, which refers to knowing whether they carry a genetic mutation in APP, PSEN1, or PSEN2. 

Genetic testing: A type of medical test that identifies if a person has any changes (such as mutations) in their DNA or genes that would cause a disease. In DIAD, genetic testing is done to find out if a person carries a mutation in APP, PSEN1, or PSEN2. 

Intrauterine insemination (IUI): (also referred to as artificial insemination). A procedure that involves placing sperm directly in the uterus. 

In-vitro fertilization (IVF): A medical procedure in which an egg is fertilized (or combined) with sperm in a test tube or outside of the body. IVF involves multiple steps or procedures that ultimately help patients with infertility issues (or genetic problems) conceive a child. 

Investigational drug: (also referred to as study or active drug). A drug that has not been approved by the U.S. Food and Drug Administration or by any other regulatory authority in countries participating in the trial. It is only available in clinical trials to determine its safety and effectiveness against a disease or medical condition. 

Natural conception: (also referred to as natural pregnancy). Natural conception occurs when a pregnancy is achieved from sexual intercourse in which sperm is ejaculated into the vagina and fertilizes an egg to create an embryo.

Non-disclosure PGT: A type of preimplantation genetic testing that involves testing embryos without disclosing or having the parents find out their genetic status or whether they carry a specific genetic mutation. An appropriate procedure for someone who doesn’t want to pass on a genetic mutation, but does not want to know if they carry the genetic mutation. 

Childbearing: Also referred to as being of reproductive age: The age in which a person is capable of bearing or fathering children. In reference to women, this often refers to women between the ages of 15-49.

Pathology: Pathology refers to the causes and effects of a disease. In Alzheimer’s disease, pathologies include amyloid plaques (the main pathology), neurofibrillary tangles, neuronal (e.g., brain cell) loss, and neuroinflammation (brain inflammation).

Placebo: A harmless substance that is given in the same manner as an investigational drug in a clinical trial. A placebo serves as a control and helps researchers understand whether a drug has a real effect on disease. An example of a placebo would be a sugar pill. 

Preimplantation genetic testing (PGT): PGT is a procedure that screens embryos for genetic abnormalities prior to being placed into a patient’s uterus. There are three main types of PGT: PGT-A, PGT-M, and PGT-SR. PGT-M or Preimplantation Genetic Testing for Monogenic Conditions, formerly known as Preimplantation Genetic Diagnosis (PGD), is the most appropriate testing for people at-risk or who carry a DIAD mutation. 

Probe (for PGT): Preimplantation genetic testing involves the creation of a custom test or probe that is tailored to identify a specific genetic mutation. 

Selective termination: (also known as selective abortion). A procedure that refers to choosing to abort a fetus, usually done when an abnormality is found in the fetus.

Study site: The physical location where a study or clinical trial is conducted. For DIAN, Washington University of St. Louis organizes the overall DIAN-TU trials, however, it enlists other universities and research centers to provide physical sites where participants can travel to be involved and participate in the trial (e.g., blood draws, MRI, PET, etc.). 

Symptom onset: In medicine, this is defined as the time a person starts showing signs of the disease. Age of symptom onset is often used in the DIAD community to determine when a family member first started showing signs of disease and helps aid researchers in understanding when other family members are eligible to join a clinical trial.  

Trial coordinator: A person responsible for carrying out activities related to conducting a clinical trial. These activities include answering calls from participants, coordinating participant study visits, working with researchers, helping participants understand the study/answering clinical trial-related questions, etc. 

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Radiation Exposure

Fertility, Reproduction, and PET Scans: A Guide for DIAN Study Participants
If you are in the DIAN study and are thinking about starting a family, it’s important to understand the possible effects of radiation from PET scans on fertility and pregnancy. This guide explains what the research says about radiation exposure, fertility, and pregnancy.

Radiation Exposure and PET Scans
Everyone receives some natural background radiation each year from sources like cosmic rays, radon, and radioactive materials in the earth. On average, this totals about 310 millirem per year in the U.S. (NCRP Report No. 160).

The three PET scans used in DIAN studies — PiB, MK-6240, and FDG — each expose you to about 350–400 millirem. This adds up to around 1,200 millirem annually from imaging, which is about four times the yearly background exposure but still far below medical or occupational exposure limits (ICRP 103, NCRP 116).

Does This Amount of Radiation Cause Cancer?
Cancer risk from radiation depends on dose and age. Most studies show that cancer risk starts to increase measurably above about 5,000 millirem (0.05 Sv), especially in children (Little et al., 2022; Berrington de Gonzalez et al., 2016). The doses from three PET scans are much lower and are considered to carry very minimal risk.

Effects on Fertility
Very high doses of radiation (more than 15,000 to 600,000 millirem) can affect fertility, depending on sex and whether exposure is temporary or ongoing. However, doses from PET scans are much lower. Transient effects on sperm production can occur at doses above 15,000 millirem, and permanent ovarian failure is not expected below 200,000 millirem (ICRP, 2007; Little et al., 2024).

Genetic Risks and Reproductive Health
Animal studies have shown that radiation can cause genetic changes, but no clear evidence of increased birth defects has been found in children of atomic bomb survivors (Ozasa et al., 2012). Human studies suggest that the risk is likely very small at low exposure levels like those from PET imaging.

When to Try to Conceive After a PET Scan
The radiotracers used in PET scans (like F-18 in FDG, PiB, and MK-6240) have short half-lives — about 2 hours for F-18 — and are cleared from the body within 24 hours (ICRP 106). It’s best to wait at least one full day before trying to conceive to reduce any potential exposure to the embryo.

What Else Can I Do?
If you are planning a pregnancy, talk to your doctor or a fertility specialist. Staying healthy with good nutrition, sleep, and stress management helps support fertility.

Conclusion
The radiation exposure from three PET scans a year is well below levels known to harm fertility or increase risk of birth defects. Waiting at least 24 hours before trying to conceive provides an extra level of safety.

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Bibliography

Berrington de Gonzalez A, et al. (2016). Radiation exposure from CT scans in childhood and subsequent risk of leukemia and brain tumors. Br J Cancer.

International Commission on Radiological Protection (ICRP). (2007). The 2007 Recommendations of the ICRP. Publication 103.

International Commission on Radiological Protection (ICRP). (2008). Radiation dose to patients from radiopharmaceuticals. ICRP Publication 106.

Little MP, et al. (2022). Review of cancer risks from low and moderate doses of sparsely ionising radiation. Environ Int.

Little MP, et al. (2024). A Historical Survey of Key Epidemiological Studies of Ionizing Radiation Exposure. Radiat Res.

National Council on Radiation Protection and Measurements (NCRP). (2009). Report No. 160.

National Council on Radiation Protection and Measurements (NCRP). (1993). Report No. 116.

Ozasa K, et al. (2012). Studies of the mortality of atomic bomb survivors. Radiat Res.

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