Time to pregnancy (TTP) is a biomarker of fecundability and has been associated with behavioral and environmental characteristics; however, these associations have not been examined in a large population-based sample of application (app) users.
Materials and Methods
This observational study followed 5,376 women with an age range of 18 to 45 years who used an app to identify their fertile window. We included women who started trying to conceive between September 30, 2017 and August 31, 2018. TTP was calculated as the number of menstrual cycles from when the user switched to "Plan" mode up to and including the cycle in which they logged a positive pregnancy test. We examined associations with several characteristics, including age, gravidity, body mass index, cycle length and cycle length variation, frequency of sexual intercourse, and temperature measuring frequency. Discrete time fecundability models were used to estimate fecundability odds ratios.
Results
For the complete cohort the 6-cycle and 12-cycle cumulative pregnancy probabilities were found to be 61% (95% confidence interval [CI]: 59-62) and 74% (95% CI: 73-76), respectively. The median TTP was four cycles. The highest fecundability was associated with an age of less than 35 years, with cycle length variation <5 days and logging sexual intercourse on at least 20% of days added (the proportion of days in which intercourse was logged) (11.5% [n = 613] of entire sample). This group achieved a 6and 12-cycle cumulative pregnancy probability of 88% (95% CI: 85-91) and 95% (95% CI: 94-97), respectively, and a TTP of 2 cycles.
Conclusions
Natural Cycles was an effective method of identifying the fertile window and a noninvasive educational option for women planning a pregnancy. Women under age 35 with regular cycles showed a high pregnancy rate.
time to pregnancy fertility app, fertility awareness mobile application, fecundability biomarker app-based, TTP behavioral characteristics, digital fertility tracking outcomes, ovulation prediction app study, natural conception fertility tracking, app-based family planning effectiveness, demographic factors time to pregnancy, environmental exposures fecundability
PMID 34495761 34495761 DOI 10.1089/jwh.2021.0026 10.1089/jwh.2021.0026
Cite this article
Favaro, C., Pearson, J. T., Rowland, S. P., Jukic, A. M., Chelstowska, M., Berglund Scherwitzl, E., Scherwitzl, R., Gemzell Danielsson, K., & Harper, J. (2021). Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy. Journal of women's health (2002), 30(11), 1538-1545. https://doi.org/10.1089/jwh.2021.0026
Favaro C, Pearson JT, Rowland SP, Jukic AM, Chelstowska M, Berglund Scherwitzl E, et al. Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy. J Womens Health (Larchmt). 2021;30(11):1538-1545. doi:10.1089/jwh.2021.0026
Favaro, C., et al. "Time to Pregnancy for Women Using a Fertility Awareness Based Mobile Application to Plan a Pregnancy." Journal of women's health (2002), vol. 30, no. 11, 2021, pp. 1538-1545.
To assess the effect of randomization to FertilityFriend.com, a mobile computing fertility-tracking app, on fecundability.
Parallel non-blinded randomized controlled trial nested within the Pregnancy Study Online (PRESTO), a North American preconception cohort. PATIENT(S): Female participants aged 21 to 45 years attempting conception for ≤6 menstrual cycles at enrolment (2013-2019). Randomization (1:1) of 5532 participants to receive a premium Fertility Friend (FF) subscription. MAIN OUTCOME MEASURE(S): 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). Using life-table methods, 64% of the 2775 participants randomized to FF and 63% of the 2767 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 enrolment. 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 enrolment, 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 enrolment (FR = 1.15; 95% CI, 0.98-1.35 for 3-4 cycles; FR = 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 enrolment (FR = 1.10; 95% CI, 1.02-1.19). 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.
Caffeine is the most frequently used psychoactive substance in the United States and >90% of reproductive-age women report some amount of intake daily. Despite biological plausibility, previous studies on caffeine and fecundability report conflicting results. Importantly, prior studies measured caffeine exposure exclusively by self-report, which is subject to measurement error and does not account for factors that influence caffeine metabolism. Our objective was to examine associations between preconception serum caffeine metabolites, caffeinated beverage intake, and fecundability. Participants included 1228 women aged 18-40 y with a history of 1-2 pregnancy losses in the EAGeR (Effects of Aspirin in Gestation and Reproduction) trial. We prospectively evaluated associations of preconception caffeine metabolites (i.e., caffeine, paraxanthine, and theobromine) measured from 1191 serum samples untimed to a specific time of day, self-reported usual caffeinated beverage intakes at baseline, and time-varying cycle-average caffeinated beverage intake, with fecundability. Using Cox proportional hazards models, we estimated fecundability odds ratios (FORs) and 95% CIs according to each metabolite. Follow-up was complete for 89% (n = 1088) of participants. At baseline, 85%, 73%, and 91% of women had detectable serum caffeine, paraxanthine, and theobromine, respectively. A total of 797 women became pregnant during ≤6 cycles of preconception follow-up. After adjusting for potential confounders, neither serum caffeine [tertile (T)3 compared with T1 0.87; 95% CI: 0.71, 1.08], paraxanthine (T3 compared with T1 0.92; 95% CI: 0.75, 1.14), nor theobromine (T3 compared with T1 1.15; 95% CI: 0.95, 1.40) were associated with fecundability. Baseline intake of total caffeinated beverages was not associated with fecundability (>3 compared with 0 0.99; 95% CI: 0.74, 1.34), nor was caffeinated coffee (>2 compared with 0 0.93; 95% CI: 0.45, 1.92) or caffeinated soda (>2 0.92; 95% CI: 0.71, 1.20). Our findings are reassuring that caffeine exposure from usual low to moderate caffeinated beverage intake likely does not influence fecundability.This trial was registered at clinicaltrials.gov as NCT00467363.
The aim of this study was to determine predictive factors for pregnancy and assess the cumulative pregnancy rate (CPR) and live birth rate (CLBR) in subfertile couples undergoing timed intercourse (TI) using ultrasound. This retrospective cohort study included 285 women (854 cycles) who started TI with ultrasound between January 2017 and October 2019. The overall clinical pregnancy rate was 28.1% (80/285) per couple and 9.4% (80/854) per cycle. Pregnant women had a higher body mass index (BMI), higher percentage of irregular menstrual cycles, a shorter duration of subfertility, lower serum follicle-stimulating hormone levels, and higher anti-Müllerian hormone levels than non-pregnant women. A longer duration of subfertility (≥24 months vs. <12 months; 0.193; 95% 0.043-0.859) and endometriosis (vs. ovulatory factors; 0.282; 95% 0.106-0.746) as causes of subfertility were unfavorable factors that independently affected clinical pregnancy. In subgroup analysis, old age ≥ 35 years [vs. < 35 years; 0.279; 95% 0.083-0.938), a longer duration of infertility ≥24 months (vs. <24 months; 0.182; 95% 0.036-0.913) and a higher BMI ≥ 25 kg/m(2)(vs. >25 kg/m(2); 3.202; 95% 1.020-10.046) in couples with ovulatory factor and a longer duration of infertility ≥24 months (vs. <24 months; 0.185; 95% 0.042-0.819) in couples with non-ovulatory factors were significant independent predictive factors for pregnancy. No significant differences were found in the cycle characteristics between pregnant and non-pregnant women. The CPR substantially increased during the first three cycles and significantly increased until the sixth cycle. No significant increase was observed in the CPR after the sixth cycle. The CLBRs substantially increased during the first three cycles and significantly increased until the fourth cycle. No significant increase was observed in the CLBRs after the fifth cycle. When comparing CPRs and CLBRs according to subfertile causes, CRPs was significantly different and CLBRs was different with borderline significance. Our findings may indicate that women with a longer duration of subfertility or subfertility due to endometriosis have poor outcomes during TI with ultrasound. Women who failed to achieve conception by the fourth or fifth cycle of TI with ultrasound may be encouraged to consider advancing to the next treatment strategy.
DeVilbiss EA et al., 2020·Paediatr Perinat Epidemiol
Attaining pregnancy is conditional upon a series of complex processes, including adequately timed intercourse, ovulation, fertilisation, and implantation. Anovulation is a first-line treatment target for couples with difficulty conceiving and is frequently examined in studies of fecundability. To identify whether sporadic anovulation is an important determinant of cumulative pregnancy rates and time to pregnancy among fertile women with regular menstrual cycles. We simulated cumulative pregnancy rates and time to pregnancy for 12 consecutive menstrual cycles among 100 000 women based on data-driven probabilities of implantation, fertilisation, ovulation, and intercourse occurring in the fertile window. We assumed anovulation probabilities of 1%, 8%, or 14.5% and intercourse averaging once per week, every other day, or daily. The model incorporated reductions in implantation and fertilisation rates for successive cycles of non-pregnancy. After 12 cycles, a reduction in the per cycle incidence of anovulation from 14.5% to 1% resulted in a 4.0% higher cumulative pregnancy rate (86.7% vs 90.7%) and similar time to pregnancy (1-cycle median difference). In contrast, increasing mean unscheduled sexual intercourse frequency from weekly to every other day was associated with a 5-cycle median reduction in time to pregnancy (weekly: 7 cycles; 2 cycles) and a 28.9% increase in the cumulative pregnancy rate (weekly: 59.9%, 88.8%; 91.6%). In presumed fertile women with regular menstrual cycles, routine investigation of anovulation may not be an informative outcome in studies of fecundability, and routine testing to ensure ovulation and treatment of anovulation are unlikely to be medically necessary. While biomarkers or cervical fluid may help time intercourse to the fertile window, time to pregnancy can also be improved through increasing the frequency of unscheduled intercourse. These findings need corroboration in large preconception time to pregnancy studies.