2026 Theses Master's

Exploring Patient Experiences with Genome Sequencing for Second and Third Trimester Pregnancy Loss to Inform Standard of Care Implementation

Sargent, Jordan; Demers, Alexandra; Adams, Sophie; Maher Trocki, Olivia; Florido, Michelle E.

Background: The genetics of pregnancy loss continues to be investigated and remains less understood in second and third trimesters. Etiology remains unknown in 25-60% of stillbirth cases and up to 50% of second trimester cases, leading to clinical and psychological uncertainty for patients and providers. Chromosomal microarray (CMA) is currently recommended as standard of care after a stillbirth, yet it only assesses large duplications and deletions and does not have the resolution to detect single gene conditions caused by sequence variants. Genome sequencing (GS) offers superior resolution of non-coding regions, improved coverage of coding regions, and the ability to detect repeat expansions and copy number variants at a higher resolution than CMA. GS further has the potential to improve understanding of the genetic etiology of stillbirth/pregnancy loss, inform recurrence risks and future clinical management decisions, and support coping. There is limited knowledge, however, around patient experiences with this technology after pregnancy loss. Purpose: The purpose of this study was to explore patient perspectives in the setting of GS following a second or third trimester pregnancy loss to provide foundational knowledge for future GS implementation by genetic counselors.

Methods: Participants were recruited from an existing cohort of 68 families who were enrolled in a primary GS study, experienced a pregnancy loss at 14 weeks of gestation or later, agreed to contact about future research, and received GS results. Semi-structured interviews were conducted by one of two members of the study team using an interview guide developed by a genetic counseling student and prenatal genetic counselors. Eight interviews were recorded and transcribed. They were coded and analyzed using a constructivist-grounded theory approach.

Results: Participants were information-seeking and described the opportunity for GS as an obvious next step, providing them with a sense of hope. However, participant opinions varied in their preference for a streamlined consent process or a delayed conversation with time to process events. This may speak to different coping methods preferred by intuitive versus instrumental grieving patterns. All participants received negative GS results, and many expressed mixed feelings of reassurance and disappointment upon disclosure, often citing feelings of guilt and blame when an etiology for their loss was not identified. Participants expressed that lengthy testing turnaround time led to increased anxiety, and clear, compassionate communication from providers was important. Additionally, many participants shared that they would be willing to confront a higher out of pocket cost for GS if the anticipated yield was high enough.

Conclusions: GS offers an opportunity to further evaluate etiologies of pregnancy loss at or greater than 14 weeks, and may provide reassurance, closure, and clinically meaningful information for families. Counseling and consent should be tailored to individual grief responses and preferences about types of information received during result disclosures. As the genomic architecture of pregnancy is further elucidated and sequencing is considered for standard of care implementation, additional research regarding patient needs in consent and results disclosure is necessary.

Keywords: pregnancy loss, stillbirth, sequencing, genetics