Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of ColumbiaROR
Department of Clinical Epidemiology Aarhus University Hospital Aarhus DenmarkROR
The aim of this study was to evaluate the association between menstrual cycle characteristics in early life and adulthood and fecundability.
Methods
Pregnancy Study Online (PRESTO) is an Internet-based preconception cohort study of pregnancy planners from the United States and Canada. During the preconception period, we enrolled 2189 female pregnancy planners aged 21-45 years who had been attempting conception for ≤6 cycles. Women self-reported menstrual cycle characteristics via an online baseline questionnaire, and pregnancy status was ascertained through bimonthly follow-up questionnaires. Proportional probabilities models were used to estimate fecundability ratios (FRs) and 95% confidence intervals (CIs), adjusting for potential confounders.
Results
Compared with usual menstrual cycle lengths of 27-29 days, cycle lengths of <25 (FR = 0.81, 95% CI: 0.54-1.22) and 25-26 days (FR = 0.92, 95% CI: 0.75-1.14) were associated with reduced fecundability. Compared with women who reached menarche at the age of 12-13 years, those who reached menarche at <12 years had reduced fecundability (FR = 0.87, 95% CI: 0.76-0.99). Women whose cycles never regularized after menarche (FR = 0.93, 95% CI: 0.81-1.06) had slightly reduced fecundability compared with women whose cycles regularized within 2 years of menarche. Bleed length and heaviness of bleeding were not appreciably associated with fecundability.
Conclusions
Menstrual cycle characteristics, specifically cycle length and age at menarche, may act as markers of fertility potential among pregnancy planners.
menstrual cycle length fecundability, irregular menstruation time to pregnancy, cycle characteristics conception probability, menarche age fertility association, menstrual regularity fecundability, PRESTO cohort menstrual cycle, dysmenorrhea fecundability, heavy menstrual bleeding fertility, menstrual cycle predictors conception, early life menstruation fertility outcomes
PMID 27449569 27449569 DOI 10.1016/j.annepidem.2016.05.006 10.1016/j.annepidem.2016.05.006
Cite this article
Wesselink, A. K., Wise, L. A., Hatch, E. E., Rothman, K. J., Mikkelsen, E. M., Stanford, J. B., McKinnon, C. J., & Mahalingaiah, S. (2016). Menstrual cycle characteristics and fecundability in a North American preconception cohort. Annals of epidemiology, 26(7), 482-487.e1. https://doi.org/10.1016/j.annepidem.2016.05.006
Wesselink AK, Wise LA, Hatch EE, Rothman KJ, Mikkelsen EM, Stanford JB, et al. Menstrual cycle characteristics and fecundability in a North American preconception cohort. Ann Epidemiol. 2016;26(7):482-487.e1. doi:10.1016/j.annepidem.2016.05.006
Wesselink, A. K., et al. "Menstrual cycle characteristics and fecundability in a North American preconception cohort." Annals of epidemiology, vol. 26, no. 7, 2016, pp. 482-487.e1.
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.
Hilgers TW, 2004·The Medical and Surgical Practice of NaProTECHNOLOGY
A CrMS-synchronized hormone sampling protocol is detailed in which progesterone, estradiol, and other reproductive hormones are drawn at cycle-phase-specific time points defined by the charted Peak Day rather than by fixed cycle day, producing a targeted hormone profile that accurately reflects luteal and follicular function. This Peak Day-referenced approach substantially improves the diagnostic sensitivity for luteal phase deficiency, follicular dysfunction, and other endocrine abnormalities that fixed-day sampling routinely misclassifies.
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.
Does sexual intercourse enhance the cycle fecundability in women without known subfertility? Sexual intercourse (regardless of timing during the cycle) was associated with cycle characteristics suggesting higher fecundability, including longer luteal phase, less premenstrual spotting and more than 2 days of cervical fluid with estrogen-stimulated qualities. Human females are spontaneous ovulators, experiencing an LH surge and ovulation cyclically, independent of copulation. Natural conception requires intercourse to occur during the fertile window of a woman's menstrual cycle, i.e. the 6-day interval ending on the day of ovulation. However, most women with normal fecundity do not ovulate on Day 14, thus the timing of the hypothetical fertile window varies within and between women. This variability is influenced by age and parity and other known or unknown elements. While the impact of sexual intercourse around the time of implantation on the probability of achieving a pregnancy has been discussed by some researchers, there are limited data regarding how sexual intercourse may influence ovulation occurrence and menstrual cycle characteristics in humans. This study is a pooled analysis of three cohorts of women, enrolled at Creighton Model FertilityCare 'Creighton Model MultiCenter Fecundability Study' (CMFS: retrospective cohort, 1990-1996), 'Time to Pregnancy in Normal Fertility' (TTP: randomized trial, 2003-2006) and 'Creighton Model Effectiveness, Intentions, and Behaviors Assessment' (CEIBA: prospective cohort, 2009-2013). We evaluated cycle phase lengths, bleeding and cervical mucus patterns and estimated the fertile window in 2564 cycles of 530 women, followed for up to 1 year. Participants were US or Canadian women aged 18-40 and not pregnant, who were heterosexually active, without known subfertility and not taking exogenous hormones. Most of the women were intending to avoid pregnancy at the start of follow-up. Women recorded daily vaginal bleeding, mucus discharge and sexual intercourse using a standardized protocol and recording system for up to 1 year, yielding 2564 cycles available for analysis. The peak day of mucus discharge (generally the last day of cervical fluid with estrogen-stimulated qualities of being clear, stretchy or slippery) was used to identify the estimated day of ovulation, which we considered the last day of the follicular phase in ovulatory cycles. We used linear mixed models to assess continuous cycle parameters including cycle, menses and cycle phase lengths, and generalized linear models using Poisson regression with robust variance to assess dichotomous outcomes such as ovulatory function, short luteal phases and presence or absence of follicular or luteal bleeding. Cycles were stratified by the presence or absence of any sexual intercourse, while adjusting for women's parity, age, recent oral contraceptive use and breast feeding. MAIN Most women were <30 years of age (75.5%; median 27, interquartile range 24-29), non-Hispanic white (88.1%), with high socioeconomic indicators and nulliparous (70.9%). Cycles with no sexual intercourse compared to cycles with at least 1 day of sexual intercourse were shorter (29.1 days (95% CI 27.6, 30.7) versus 30.1 days (95% CI 28.7, 31.4)), had shorter luteal phases (10.8 days (95% CI 10.2, 11.5) versus 11.4 days (95% CI 10.9, 12.0)), had a higher probability of luteal phase deficiency (<10 days; adjusted probability ratio (PR) 1.31 (95% CI 1.00, 1.71)), had a higher probability of 2 days of premenstrual spotting (adjusted PR 2.15 (95% CI 1.09, 4.24)) and a higher probability of having two or fewer days of peak-type (estrogenic) cervical fluid (adjusted PR 1.49 (95% CI 1.03, 2.15)). LIMITATIONS Our study participants were geographically dispersed but relatively homogeneous in regard to race, ethnicity, income and educational levels, and all had male partners, which may limit the generalizability of the findings. We cannot exclude the possibility of undetected subfertility or related gynecologic disorders among some of the women, such as undetected endometriosis or polycystic ovary syndrome, which would impact the generalizability of our findings. Acute illness or stressful events might have reduced the likelihood of any intercourse during a cycle, while also altering cycle characteristics. Some cycles in the no intercourse group may have actually had undocumented intercourse or other sexual activity, but this would bias our results toward the null. The Creighton Model FertilityCare System (CrM) discourages use of barrier methods, so we believe that most instances of intercourse involved exposure to semen; however, condoms may have been used in some cycles. Our dataset lacks any information about the occurrence of female orgasm, precluding our ability to evaluate the independent or combined impact of female orgasm on cycle characteristics. Sexual activity may change reproductive hormonal patterns, and/or levels of reproductive hormones may influence the likelihood of sexual activity. Future work may help with understanding the extent to which exposure to seminal fluid, and/or female orgasm and/or timing of intercourse could impact menstrual cycle function. In theory, large data sets from women using menstrual and fertility tracking apps could be informative if women can be appropriately incentivized to record intercourse completely. It is also of interest to understand how cycle characteristics may differ in women with gynecological problems or subfertility. Funding for the research on the three cohorts analyzed in this study was provided by the Robert Wood Johnson Foundation #029258 (Creighton Model MultiCenter Fecundability Study), the Eunice Kennedy Shriver National Institute of Child Health and Human Development 1K23 HD0147901-01A1 (Time to Pregnancy in Normal Fertility) and the Office of Family Planning, Office of Population Affairs, Health and Human Services 1FPRPA006035 (Creighton Model Effectiveness, Intentions, and Behaviors Assessment). The authors declare that they have no conflict of interest. N/A.