Background Medically assisted reproduction (MAR) is a challenging application area for health economic evaluations, entailing a broad range of costs and outcomes, stretching out long-term and accruing to several parties. Purpose To systematically review which costs and outcomes are included in published economic evaluations of MAR and to compare these with health technology assessment (HTA) prescriptions about which cost and outcomes should be considered for different evaluation objectives. Data Sources HTA guidelines and systematic searches of PubMed Central, Embase, WOS CC, CINAHL, Cochrane (CENTRAL), HTA, and NHS EED. Study Selection All economic evaluations of MAR published from 2010 to 2022. Data Extraction A predetermined data collection form summarized study characteristics. Essential costs and outcomes of MAR were listed based on HTA and treatment guidelines for different evaluation objectives. For each study, included costs and outcomes were reviewed. Data Synthesis The review identified 93 cost-effectiveness estimates, of which 57% were expressed as cost-per-(healthy)-live-birth, 19% as cost-per-pregnancy, and 47% adopted a clinic perspective. Few adopted societal perspectives and only 2% used quality-adjusted life-years (QALYs). Broader evaluations omitted various relevant costs and outcomes related to MAR. There are several cost and outcome categories for which available HTA guidelines do not provide conclusive directions regarding inclusion or exclusion. Limitations Studies published before 2010 and of interventions not clearly labeled as MAR were excluded. We focus on methods rather than which MAR treatments are cost-effective. Conclusions Economic evaluations of MAR typically calculate a short-term cost-per-live-birth from a clinic perspective. Broader analyses, using cost-per-QALY or BCRs from societal perspectives, considering the full scope of reproduction-related costs and outcomes, are scarce and often incomplete. We provide a summary of costs and outcomes for future research guidance and identify areas requiring HTA methodological development. Highlights The cost-effectiveness of MAR procedures can be exceptionally complex to estimate as there is a broad range of costs and outcomes involved, in principle stretching out over multiple generations and over many stakeholders. We list 21 key areas of costs and outcomes of MAR. Which of these needs to be accounted for alters for different evaluation objectives (determined by the type of economic evaluation, time horizon considered, and perspective). Published studies mostly investigate cost-effectiveness in the very short-term, from a clinic perspective, expressed as cost-per-live-birth. There is a lack of comprehensive economic evaluations that adopt a broader perspective with a longer time horizon. The broader the evaluation objective, the more relevant costs and outcomes were excluded. For several costs and outcomes, particularly those relevant for broader, societal evaluations of MAR, the inclusion or exclusion is theoretically ambiguous, and HTA guidelines do not offer sufficient guidance.
