STUDY QUESTION Can animation videos on how to optimize the chances of pregnancy influence stress, anxiety, depression and sexual functioning of individuals trying to conceive (TTC)? SUMMARY ANSWER There were no differences between those educated to have intercourse every other day, on the fertile window and a control group (CG), and depression and sexual dysfunction significantly increased over time for all arms. WHAT IS KNOWN ALREADY Recent findings indicate that time to pregnancy can be significantly shortened by targeting the fertile period, but some reproductive care guidelines recommend instead the practice of intercourse every other day on the basis that it is less stressful to the couple. Evidence to support guidelines on how to preserve well-being and psychosocial adjustment and optimize pregnancy chances is lacking. STUDY DESIGN, SIZE, DURATION We conducted a prospective, double-blinded, three-arm randomized controlled trial between July 2016 and November 2019. Participants were randomized to either not having any stimulus (CG) or visualizing a short animated video explaining how to improve chances of pregnancy by having intercourse every other day (EOD group), or by monitoring the fertile window (FWM group). Assessments were made before the intervention (T0), and 6 weeks (T1), 6 months (T2) and 12 months after (T3), with follow-ups censored in case of pregnancy. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants were childless individuals of reproductive age actively TTC and not diagnosed or unaware of a condition that could prevent spontaneous pregnancy. Individuals were excluded from recruitment if they had previous children or had a condition preventing spontaneous pregnancy. Our primary outcome was stress and secondary outcomes included anxiety, depression, sexual functioning and pregnancy. Primary analyses were performed according to intention-to-treat principle. MAIN RESULTS AND THE ROLE OF CHANCE Of the 450 randomized participants 127 were educated to use an every-other-day strategy, 135 to monitor the fertile window, and 134 received no intervention. Groups were similar regarding demographics and months TTC. Repeated measures analysis revealed that there were no significant interaction effects of psychological and sexual well-being between groups over time (P > 0.05). Significant time effects were revealed for stress (F(3,855) = 4.94, P < 0.01), depression (F(3,855) = 14.22, P < 0.01) and sexual functioning (time effects P values 0.05). Stress levels lowered after 6 months (P < 0.001) and returned to baseline levels at the 1-year follow-up. Depressive symptomatology significantly increased at 6 weeks (P = 0.023), and again 1 year after (P = 0.001). There were also significant decreases in all female sexual functioning dimensions (desire, satisfaction, arousal, pain, orgasm and lubrication). In men, there were significant variations in orgasm, intercourse satisfaction and erectile function, but not desire and sexual satisfaction. Revealed pregnancy rates were 16% for participants in the EOD group, 30% for the FWM group and 20% for the CG. Pregnancies were not significantly different between arms: EOD vs FWM (odds ratio (OR) 2.32; 95% CI 0.92-5.83); EOD vs CG (OR 0.74; 95% CI 0.30-1.87); and FWM vs CG (OR 1.71; 95% CI 0.70-4.18). LIMITATIONS, REASONS FOR CAUTION Participants were recruited after transitioning to procreative sex.

The study might be prone to bias as almost 30% of our sample fulfilled the chronological criterion for infertility, and other reproductive strategies could have been tried over time before recruitment. WIDER IMPLICATIONS OF THE FINDINGS Our data suggest that stress does not arise from feeling pressured on the fertile period and that advice on timing of intercourse might have to be personalized. The increasing levels of depression and sexual dysfunction over a year emphasize the crucial role of preconception care and fertility counseling in promoting psychological and sexual well-being. STUDY FUNDING/COMPETING INTEREST(S) This work was supported by European Union Funds (FEDER/COMPETE-Operational Competitiveness Programme) and by national funds (FCT-Portuguese Foundation for Science and Technology) under the projects PTDC/MHC-PSC/4195/2012 and SFRH/BPD/85789/2012.

DATE OF FIRST PATIENT'S ENROLLMENT 19 July 2016