BACKGROUND: Fertility treatment is not guaranteed to succeed and around 30% of patients do not achieve parenthood. Failed treatment represents the loss of parenthood and often triggers intense and prolonged grief reactions. There is an increasing awareness of the need to support patients in the aftermath of failed treatment; however, there are no effective interventions for the effect. This need for support is expected to increase as the number of people delaying parenthood increases and therefore so does the number for whom assisted reproduction will not offer a solution. OBJECTIVE AND RATIONALE: This mixed-methods review aims at investigating if patients with failed fertility treatment experience significant psychosocial adjustment difficulties that warrant the provision of psychosocial support, and at developing a comprehensive model of adjustment to unmet parenthood goals that can be used to assist the design of theory led psychosocial interventions. SEARCH METHODS: Five databases were systematically searched between 1978 and December 2015. Search terms were variations of fertility treatment AND psychosocial adjustment AND post-treatment. Quantitative studies had to include group mean comparisons on psychosocial adjustment (mental-health and well-being) between patients who had failed treatment and a control group. Qualitative studies had to focus on experiences of psychosocial adjustment after failed treatment. Screening, data extraction and critical appraisal were carried out independently by the authors using predefined protocols. Two meta-analyses were performed on mental-health and well-being with a random effect model. The primary outcome was Hedge's g. Publication bias was checked with visual inspection of funnel plots, Egger's test and the trim-and-fill method. A three-stage thematic analysis of results reported in primary qualitative papers was implemented. Firstorder descriptive and second-order interpretative themes were extracted. OUTCOMES: Nine quantitative (9052 individuals, 8 countries) and 9 qualitative (267 individuals, 6 countries) studies were included. Six (67%) of the quantitative studies reported on mental-health and six on well-being. The meta-analyses showed that the failed group had worse mental-health (g = -0.496, P = 0.001, 95% CI [-0.791 to 0.200]; I-2 = 88%, P < 0.001) and well-being (g = -0.324, P < 0.001, 95% CI [-0.454 to 0.193], I-2 = 0%, P = 0.552) than controls. The qualitative review resulted in 28 first-order themes that were grouped into 6 second-order themes: individual and relational adjustment, social adjustment, acceptance, pursuit of new life goals, meaning making, and fertility care perceptions and needs. The data showed that individual, relational and social adjustment tended to increase with time since treatment, and that individuals' care perceptions and needs also changed. The data also suggested that individuals who engage in the psychological tasks of accepting and making meaning of their situation and pursuing new life goals adjust better and have fewer support needs. These predictions were articulated in the Three Tasks Model of Adjustment to Unmet Parenthood Goals. WIDER IMPLICATIONS: Results provide compelling evidence for the provision of psychosocial care directed at helping individuals who are relinquishing their parenthood goals. The Three Tasks Model of Adjustment to Unmet Parenthood Goals offers comprehensive guidance on the therapeutic mechanisms that psychosocial care should target to promote adjustment. Future research should test the model with prospective cohort studies or by developing and testing interventions based on its predictions.