Reproductive Decision-Making for X-linked Heterozygotes: Unexplored Complexities

Abstract

Background: Reproductive decision-making (RDM) is known to be a complex process, especially for heterozygotes with a pathogenic X-linked genetic variant. While studies of carriers of genetic conditions with various inheritance patterns have identified some personal values and concerns relevant to reproductive decisions, the ways in which X-linked heterozygotes (XLHs) integrate personal values, concerns, and the influence of social relationships into their decision-making process has not been fully understood, especially in the context of rare diseases. Objective: This study aims 1) to characterize what is currently known about RDM for XLHs, and 2) to further our current understanding by exploring experiences of RDM in heterozygotes from a community with a rare X-linked disease community, Barth syndrome. Methods: The first objective was met by conducting a scoping review of the values and psychosocial experiences that influenced the RDM process for XLHs. To address the second objective, previously conducted semi-structured interviews with 27 women with X-linked tafazzin variants recruited through the Barth Syndrome Foundation were analyzed. While these interviews included questions about psychological challenges, RDM experiences, and support systems of XLHs, secondary data analysis primarily addressed decisional conflict (DC) during RDM. Results: 84 articles met inclusion criteria for the scoping review. Analysis of these articles showed that negative emotions like guilt, fear, and anxiety often accompanied RDM. Values like spirituality, conservation of personal resources, and a desire to avoid causing suffering were especially influential. Secondary data analysis made clear that XLHs are highly susceptible to DC during RDM due to extra reproductive considerations related to the possible transmission of a genetic variant. Facing these considerations could lead to negative emotions and DC when personal values conflicted with other personal values or the opinions of others. To resolve the conflict, heterozygotes re-prioritized their values, reconsidered the extent to which they allowed certain values to influence reproductive decisions, and altered the content of their values. Discussion: Many of the values identified in the scoping review were also named by Barth heterozygotes, suggesting that the manuscript findings are generalizable to other XLHs. Genetic counselors should offer decisional and emotional support to XLHs at multiple points throughout the RDM process.