Experiences and Outcomes of Fertility Testing in Male Adolescents and Young Adults with Sickle Cell Disease

Introduction:

Most adolescents and young adults (AYAs) with sickle cell disease (SCD) desire future biological parenthood. Recent research shows abnormal semen parameters in men with SCD, yet few studies have been conducted to elucidate fertility related impacts of SCD and its treatments among male AYAs with SCD. AYAs face many barriers to receiving care that could also impact their ability to complete fertility testing (i.e., via semen analysis). Thus, the aims of this study were to: 1) assess the feasibility of obtaining semen samples at a reproductive diagnostic center from male AYAs with SCD, 2) describe AYAs' and caregivers' experiences with testing, and 3) examine semen parameters among AYAs who completed testing.

Methods

Male AYAs with SCD (14-22 years, any genotype) and their caregivers were recruited to a single site study from November 2022-April 2023; the protocol involved completion of a novel web-based reproductive health program (i.e., FUTURES) describing potential fertility-related aspects of SCD and its treatments. AYA participants ≥18 years of age and AYA-caregiver dyads (if the AYA was <18 years old) were subsequently informed of the option for the AYA to obtain a semen analysis at an off-site reproductive diagnostic center (with costs of testing and transportation covered). Up to three attempts were made to contact AYA participants about their interest in testing. If interested, an order was sent to the testing center who then coordinated testing with the AYA. Research staff made up to three attempts to follow up with AYAs who reported interest but did complete testing. AYAs (and caregivers, if <18) who completed testing were notified of their results by a hematologist and invited to complete a facilitators interview. AYAs (and caregivers, if <18) who did not complete testing were invited to complete a barriers interview. Research staff conducted, transcribed, and analyzed interview transcripts for themes that demonstrated strong interrater reliability (κ=.94). Testing was considered feasible if ≥25% of AYAs completed testing. Demographic and treatment characteristics were abstracted from the medical record.

Results

Thirty-three AYAs completed FUTURES; five (15%) completed testing (Table 1) and a facilitators interview. Ten AYAs completed a barriers interview. Of the 18 enrolled caregivers, one completed a facilitators interview and seven completed a barriers interview.

Facilitators included: 1) interest in learning about reproductive health [“ I told him ... sometimes people don't know if it is too late {to have a biological child} and if we checked we could have done something about it.” - Caregiver], 2) assistance coordinating testing appointments [“ Helping to coordinate {made testing easier} because I kept on missing the appointments.” -AYA] 3) alleviating costs [“ It {the funding} helped a lot because they {research team} had to pay and we didn't have to worry about it.” - Caregiver].

Barriers included: 1) discomfort [“ I don't think anything could have helped with the decision... he was just a little uncomfortable.” -Caregiver], 2) time [“ It is something I'm interested in, but not at the moment. I'm catching up on a lot of things.” -AYA], 3) transportation [e.g., “ I don't have a car. I didn't have a way to get there.” -AYA], and 4) forgetting the appointment [“ We just forgot about the appointment.” -Caregiver].

Conclusions

Despite providing reproductive health education, compensation, and access to a local testing center, obtaining semen samples at an offsite center from male AYAs with SCD was not feasible. Abnormal semen parameters were noted across genotypes. While azoospermia and cryptozoospermia were noted in those on prolonged hydroxyurea treatment, oligospermia was also found in an individual with less severe disease and no hydroxyurea exposure. These findings underscore the importance of larger, longitudinal studies to examine semen parameters in male AYAs with SCD, ideally starting in mid-puberty. Further, qualitative findings highlight the need for: 1) developmentally and culturally appropriate fertility education, 2) innovative methods to collect semen samples (e.g., mail-in testing), and 3) advocacy to increase access to affordable reproductive healthcare. This is crucial to elucidate the fertility impacts of SCD and hydroxyurea and because the curative options that can also affect fertility are expanding for this underserved minority population.