There are four basic ethical principles in medicine: autonomy, beneficence, nonmaleficence, and justice. To protect human subjects during clinical research, informed consent is crucial to achieving these principles, which involves informing subjects of their rights, alternative treatment options, risks, and benefits prior to their trial participation. In the ADND field, we believe there is a current gap regarding ethical considerations and patient fertility, particularly informed consent and the measures taken to adequately address and acknowledge the potential risk to trial participants’ fertility during their participation in trials testing investigational treatments with unknown risk. In oncology, studies show that providing information to patients about treatment-associated reproductive risks is integral to helping them make informed decisions . Fertility preservation discussions with health care professionals increases patient understanding of the consequences of their disease/treatment on fertility and elevates patient satisfaction with their health care [7, 9].
In ADND prevention trials, there is limited information on whether investigational drugs undergo testing for fertility-related effects, and whether this data is disclosed to patients. Although these experimental drugs are primarily brain-directed, some prevention trials are currently exploring systemic interventions given orally or intravenously. Thus, it is critically important, and necessary for adequate informed consent, for investigators to provide patients with data on the impact of these experimental drugs on egg supply, sperm health, teratogenicity, and fetal neurodevelopment, or the lack thereof. While an argument could be made that investigational trials should be held until the effects of these drugs on fertility are known, the desire for disease-modifying treatments within the ADND field cannot be overstated. Clinical trial participation forces patients to confront and weigh the importance of many major life situations and decisions: their desire to have biological children, their disease age of onset, their remaining natural fertility window, and the promise of an investigational drug to modify disease pathology (Fig. 1). In addition, if ADND prevention trials include long periods of open label extension or require drug treatment for the lifetime of the patient, patients could lose childbearing capacity due to an extended delay in reproduction (as a result of longer trial participation). This could also result in less disease-free time raising their yet unborn children, reducing quality time spent together. Furthermore, the patient must also consider the chance of their assignment to a placebo group in the investigational trial, and whether contributing to a clinical trial (without receiving potential disease intervention) outweighs the potential loss of fertile years. Without proper discussion of these issues, patient drop-off rates could increase as patients realize their desire to have a biological child outweighs their desire stay in a clinical trial; or patients could feel pressured to stay in a trial longer than they had anticipated and unexpectedly lose out on critical fertility years. Thus, prior to trial enrollment, it is critical to: inform the patient of drug/trial-associated fertility risks, ensure patients understand that treatment-associated fertility holds may overlap with years of successful reproduction, consult patients about fertility preservation options (oocyte/sperm cryopreservation and/or surrogacy)—including a discussion of the costs (both physical and emotional burden) and success rates of assisted reproduction technology (if gamete cryopreservation is chosen), and provide treatment options to facilitate patient pursuance of family planning and childbearing as desired. To ensure that ADND patients have the information necessary to make an informed choice when joining preventative trials, we urge investigators to provide ADND patients with information of temporal and biological trial-related risks to participants’ fertility.