OBJECTIVE: To assess the effect of randomization to FertilityFriend.com (FF), a mobile computing fertility-tracking app, on fecundability.
DESIGN: Parallel non-blinded randomized controlled trial nested within Pregnancy Study Online (PRESTO), a North American preconception cohort.
SUBJECTS: Female participants aged 21-45 years attempting conception for ≤6 menstrual cycles at enrollment (2013-2019).
INTERVENTION: Randomization (1:1) of 5,532 participants to receive a premium FF subscription.
MAIN OUTCOME MEASURES: Fecundability (per-cycle probability of conception). Participants completed bimonthly follow-up questionnaires until pregnancy or a censoring event, whichever came first. We first performed an intent-to-treat analysis of the effect of FF randomization on fecundability. In secondary analyses, we used a per-protocol approach that accounted for adherence in each trial arm. In both analyses, we used proportional probabilities regression models to estimate fecundability ratios (FR) and 95% confidence intervals (CI) comparing those randomized vs. not randomized, and applied inverse probability weights to account for loss-to-follow-up (intent-to-treat and per-protocol analyses) and adherence (per-protocol analyses only).
RESULTS: Using life-table methods, 64% of the 2,775 participants randomized to FF and 63% of the 2,767 participants not randomized to FF conceived during 12 cycles; these respective percentages were each 70% among those with 0-1 cycles of attempt time at enrollment. Of those randomized to FF, 72% were defined as adherent (68% of observed menstrual cycles). In intent-to-treat analyses, there was no appreciable association overall (FR=0.97, 95% CI: 0.90-1.04) or within strata of pregnancy attempt time at enrollment, age, education, or other characteristics. In per-protocol analyses, we observed little association overall (FR=1.06, 95% CI: 0.99-1.14), but weak-to-moderate positive associations among participants who had longer attempt times at enrollment (FR=1.15, 95% CI: 0.98-1.35 for 3-4 cycles; 1.14, 95% CI: 0.87-1.48 for 5-6 cycles), were aged <25 years (FR=1.29, 95% CI: 1.01-1.66), had ≤12 years of education (FR=1.32, 95% CI: 0.92-1.89), or were non-users of hormonal contraception within 3 months before enrollment (FR=1.10, 95% CI: 1.02-1.19).
CONCLUSION: No appreciable associations were observed in intent-to-treat analyses. In secondary per-protocol analyses that accounted for adherence, randomization to FF was associated with slightly greater fecundability among selected subgroups of participants; however, these results are susceptible to unmeasured confounding.
