Wise, L. A., Rothman, K. J., Mikkelsen, E. M., Sørensen, H. T., Riis, A., & Hatch, E. E. (2010). An internet-based prospective study of body size and time-to-pregnancy. Human reproduction (Oxford, England), 25(1), 253-264. https://doi.org/10.1093/humrep/dep360
Wise LA, Rothman KJ, Mikkelsen EM, Sørensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod. 2010;25(1):253-264. doi:10.1093/humrep/dep360
Wise, L. A., et al. "An internet-based prospective study of body size and time-to-pregnancy." Human reproduction (Oxford, England), vol. 25, no. 1, 2010, pp. 253-264.
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3 institutions
Slone Epidemiology Center at Boston University, Boston, Massachusetts and 2Lombardi Comprehensive Cancer Center at Georgetown University Medical Center, Washington, District of Columbia05vzafd60
Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA05qwgg493
Department of Clinical Epidemiology Aarhus University Hospital Aarhus Denmark040r8fr65
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Abstract
Background
Recent studies have shown that both female and male obesity may delay time-to-pregnancy (TTP). Little is known about central adiposity or weight gain and fecundability in women.
Methods
We examined the association between anthropometric factors and TTP among 1651 Danish women participating in an internet-based prospective cohort study of pregnancy planners (2007-2008). We categorized body mass index (BMI = kg/m(2)) as underweight (<20), normal weight (20-24), overweight (25-29), obese (30-34) and very obese (> or =35). We used discrete-time Cox regression to estimate fecundability ratios (FRs) and 95% confidence intervals (CI), controlling for potential confounders.
Results
We found longer TTPs for overweight (FR = 0.83, 95% CI = 0.70-1.00), obese (FR = 0.75, 95% CI = 0.58-0.97), and very obese (FR = 0.61, 95% CI = 0.42-0.88) women, compared with normal weight women. After further control for waist circumference, FRs for overweight, obese, and very obese women were 0.72 (95% CI = 0.58-0.90), 0.60 (95% CI = 0.42-0.85) and 0.48 (95% CI = 0.31-0.74), respectively. Underweight was associated with reduced fecundability among nulliparous women (FR = 0.82, 95% CI = 0.63-1.06) and increased fecundability among parous women (FR = 1.61, 95% CI = 1.08-2.39). Male BMI was not materially associated with TTP after control for female BMI. Compared with women who maintained a stable weight since age 17 (-5 to 4 kg), women who gained > or =15 kg had longer TTPs (FR = 0.72, 95% CI = 0.59-0.88) after adjustment for BMI at age 17. Associations of waist circumference and waist-to-hip ratio with TTP depended on adjustment for female BMI: null associations were observed before adjustment for BMI and weakly positive associations were observed after adjustment for BMI.
Conclusions
Our results confirm previous studies showing reduced fertility in overweight and obese women. The association between underweight and fecundability varied by parity.
Velmahos AH et al., 2026·Journal of Restorative Reproductive Medicine·Free to read
To evaluate the extent to which a history of infertility is associated with adherence to specific diets among reproductive-aged females. Cross-sectional analysis Between 2017–2023, 7,227 North American female pregnancy planners aged 21-45 years enrolled in PRESTO (Pregnancy Study Online), a preconception cohort study. Participants completed self-administered baseline questionnaires during preconception. Exposure: Infertility history, defined as: 1) self-reported 12-month clinical infertility, 2) history of visiting a clinician for an infertility work-up, and/or 3) clinician-identified cause of infertility (e.g., ovulatory or tubal). Adherence to specific diets, including vegetarian, vegan, Mediterranean, Paleo, Weight Watchers®, ketogenic, dairy free, gluten free, Atkins®, South Beach®, Zone®, raw foods, or other at baseline. Multivariable log-binomial regression models estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs), adjusted for age, income, and body mass index (BMI). The percentage of participants with a history of infertility was 26% based on the 12-month clinical infertility definition, 30% based on visiting a physician for infertility evaluation, and 26% based on an infertility diagnosis following a physician visit. Overall adherence to any particular diet was low (4.6% vegetarian, 2.8% ketogenic, 1.7% Weight Watchers®, 1.4% Mediterranean, 1.3% vegan, 0.8% Paleo, and all other diets: <0.8%); 86.6% reported not adhering to any particular diet. A history of 12-month clinical infertility was associated with lower adherence to vegetarian (PR=0.78; 95% CI: 0.60-1.03), Paleo (PR=0.43; 95% CI: 0.19-0.98), and Weight Watchers® (PR=0.55; 95% CI: 0.34-0.91) diets. An infertility history involving a medical work-up was associated with a higher prevalence of adherence to a ketogenic diet (PR=1.56; 95% CI: 1.17-2.09). Participants whose infertility was attributed to ovulatory or tubal causes were nearly two times more likely to adhere to a ketogenic diet (PR=2.01; 95% CI: 1.38-2.94; PR=2.22; 95% CI: 1.09-4.49, respectively). The cross-sectional design cannot establish temporality or causality. Data on dietary patterns and infertility history were self-reported, which can introduce misclassification. Generalizability may be limited because participants were pregnancy planners not using fertility treatments; participants were also more likely to be non-Hispanic White and of higher socioeconomic status than the general population. The ketogenic diet was more prevalent among females with an infertility history, while vegetarian, Paleo, and Weight Watchers® diets were less prevalent. These associations mirror the results of studies evaluating the reverse relationship, suggesting that some patients with infertility seek information for behavioral modifications via evidence-based medicine.
Pedersen ES et al., 2024·Paediatr Perinat Epidemiol·Free full text on PubMed Central
The use of fertility indicators to predict ovulation has largely been studied for contraceptive purposes, while less so as fertility-promoting tools. To investigate the association between fertility indicators and fecundability in Danish women trying to conceive. Web-based preconception cohort study. We analysed data from 11,328 females aged 18-49 years trying to conceive without fertility treatment for ≤6 menstrual cycles, from the Danish SnartGravid.dk and SnartForældre.dk cohorts (2007-2023). Participants reported the use of fertility indicators (counting days since the last menstrual period, cervical fluid monitoring, urinary ovulation testing, feeling ovulation, using a smartphone fertility app and measuring basal body temperature [BBT]). Time to pregnancy was measured in menstrual cycles ascertained by self-reported pregnancy status. We estimated fecundability ratios (FR) and 95% confidence intervals (CI) using proportional probabilities regression models adjusted for age, socio-economic position, health indicators, reproductive history and gynaecological factors. Fertility indicators were used by 63.3% of participants at study entry. Counting days was the most common (46.9%), while measuring BBT was the least (3.0%). Other indicators ranged from 17.0% to 23.6%, with 69.7% using more than one indicator. Compared with non-use, use of any fertility indicator was associated with greater fecundability (adjusted FR 1.14, 95% CI 1.08, 1.19). Cervical fluid monitoring showed the strongest association (aFR 1.46, 95% CI 1.03, 2.07), followed by urinary ovulation testing (aFR 1.35, 95% CI 1.16, 1.58) and counting days (aFR 1.18, 95% CI 1.09, 1.29). Feeling ovulation and fertility apps were modestly associated with fecundability, while measuring BBT was not associated. Sensitivity analysis restricting to ≤2 cycles of attempt time and two cycles of follow-up showed an aFR for any indicator use of 1.21 (95% CI 1.13, 1.31). In this Danish preconception cohort, use of fertility indicators was associated with a higher fecundability, varying by type of indicator.
Mitro SD et al., 2024·JAMA network open·Free full text on PubMed Central
Fibroids are benign neoplasms associated with severe gynecologic morbidity. There are no strategies to prevent fibroid development. To examine associations of hypertension, antihypertensive treatment, anthropometry, and blood biomarkers with incidence of reported fibroid diagnosis in midlife. DESIGN, SETTING, The Study of Women's Health Across the Nation is a prospective, multisite cohort study in the US. Participants were followed-up from enrollment (1996-1997) through 13 semiannual visits (1998-2013). Participants had a menstrual period in the last 3 months, were not pregnant or lactating, were aged 42 to 52 years, were not using hormones, and had a uterus and at least 1 ovary. Participants with prior fibroid diagnoses were excluded. Data analysis was performed from November 2022 to February 2024. Blood pressure, anthropometry, biomarkers (cholesterol, triglycerides, and C-reactive protein), and self-reported antihypertensive treatment at baseline and follow-up visits were measured. Hypertension status (new-onset, preexisting, or never [reference]) and hypertension treatment (untreated, treated, or no hypertension [reference]) were categorized. Participants reported fibroid diagnosis at each visit. Discrete-time survival models estimated hazard ratios (HRs) and 95% CIs for associations of time-varying hypertension status, antihypertensive treatment, anthropometry, and biomarkers with incident reported fibroid diagnoses. Among 2570 participants without a history of diagnosed fibroids (median [IQR] age at screening, 45 [43-48] years; 1079 [42.1%] college educated), 526 (20%) reported a new fibroid diagnosis during follow-up. Risk varied by category of hypertension treatment: compared with those with no hypertension, participants with untreated hypertension had a 19% greater risk of newly diagnosed fibroids (HR, 1.19; 95% CI, 0.91-1.57), whereas those with treated hypertension had a 20% lower risk (HR, 0.80; 95% CI, 0.56-1.15). Among eligible participants with hypertension, those taking antihypertensive treatment had a 37% lower risk of newly diagnosed fibroids (HR, 0.63; 95% CI, 0.38-1.05). Risk also varied by hypertension status: compared with never-hypertensive participants, participants with new-onset hypertension had 45% greater risk of newly diagnosed fibroids (HR, 1.45; 95% CI, 0.96-2.20). Anthropometric factors and blood biomarkers were not associated with fibroid risk. Participants with untreated and new-onset hypertension had increased risk of newly diagnosed fibroids, whereas those taking antihypertensive treatment had lower risk, suggesting that blood pressure control may provide new strategies for fibroid prevention.
Wise LA et al., 2023·Fertil Steril·Free full text on PubMed Central
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.
Related research
Nutrition and Metabolic Health · Body Weight and Composition
To investigate the association between pre-pregnancy body mass index (BMI) and subfertility within a population-based cohort, exploring Hispanic ethnicity as a potential effect modifier. We used cross-sectional study data from the Utah Pregnancy Risk Assessment Monitoring System from 2012-2015. Relationships between maternal pre-pregnancy BMI and subfertility were evaluated via Poisson regression models with robust error variance, accounting for the stratified survey sampling. Preconception BMI was analyzed continuously and categorically. Women's subfertility was defined via self-report in two ways: 1) time trying to achieve pregnancy; and 2) report of using fertility-related drugs/medical procedures. The median age was 27.0; 18.8% were obese, and 15.9% were Hispanic. Women with preconception obesity (BMI>30kg/m(2)), compared to normal weight women (18.4kg/ m(2)<BMI<25kg/m(2)) had a 1.85 (95% CI 1.43, 2.38) higher adjusted prevalence ratio (aPR) for having subfertility defined by time trying and a 1.73 (95% CI 1.20, 2.32) higher aPR for receiving fertility-enhancing drugs/medical procedures. Continuous models indicated a linear relationship between BMI and subfertility (aPR 1.04, 95% CI 1.03, 1.06 for time trying; and 1.06, 95% CI 1.03, 1.10 for receiving fertility-enhancing drugs/medical procedures). Obese women, but not underweight or overweight women, reported higher subfertility than normal-weight women. Findings among this cohort of at-risk new mothers, oversampled on low education and birth weight and comprised of higher than the national average of Hispanics, indicated a dose-response relationship between obesity and subfertility.
Our findings highlight the importance of population-oriented obesity prevention for at-risk women with intentions to conceive.
Russo LM et al., 2018·Hum Reprod·Free full text on PubMed Central
Is physical activity (PA) associated with fecundability in women with a history of prior pregnancy loss? Higher fecundability was related to walking among overweight/obese women and to vigorous PA in women overall. PA may influence fecundability through altered endocrine function. Studies evaluating this association have primarily utilized Internet-based recruitment and self-report for pregnancy assessment and have yielded conflicting results. STUDY DESIGN, SIZE, Duration: This is a secondary analysis of the Effects of Aspirin in Gestation and Reproduction (EAGeR) trial (2007-2011), a multisite, randomized controlled trial of preconception-initiated low-dose aspirin. PARTICIPANTS/MATERIALS, SETTING, Healthy women (n = 1214), aged 18-40 and with 1-2 prior pregnancy losses, were recruited from four US medical centers. Participants were followed for up to six menstrual cycles while attempting pregnancy and through pregnancy for those who became pregnant. Time to hCG detected pregnancy was assessed using discrete-time Cox proportional hazard models to estimate fecundability odds ratios (FOR) adjusted for covariates, accounting for left truncation and right censoring. Main The association of walking with fecundability varied significantly by BMI (P-interaction = 0.01). Among overweight/obese women, walking ≥10 min at a time was related to improved fecundability (FOR = 1.82, 95% CI: 1.19, 2.77). In adjusted models, women reporting >4 h/wk of vigorous activity had significantly higher fecundability (FOR = 1.69, 95% CI: 1.24, 2.31) compared to no vigorous activity. Associations of vigorous activity with fecundability were not significantly different by BMI (P-interaction = 0.9). Moderate activity, sitting, and International Physical Activity Questionnaire (IPAQ) categories were not associated with fecundability overall or in BMI-stratified analyses. LIMITATIONS, Some misclassification of PA levels as determined by the short form of the IPAQ is likely to have occurred, and may have led to non-differential misclassification of exposure in our study. Information on diet and change in BMI was not collected and may have contributed to some residual confounding in our results. The generalizability of our results may be limited as our population consisted of women with a history of one or two pregnancy losses. These findings provide positive evidence for the benefits of PA in women attempting pregnancy, especially for walking among those with higher BMI. Further study is necessary to clarify possible mechanisms through which walking and vigorous activity might affect time-to-pregnancy. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The authors report no conflicts of interest in this work. #NCT00467363.
Schliep KC et al., 2015·Fertil Steril·Free full text on PubMed Central
To assess the effects of both male and female body mass index (BMI), individually and combined, on IVF outcomes.
Prospective cohort study.
University fertility center. PATIENT(S): All couples undergoing first fresh IVF cycles, 2005-2010, for whom male and female weight and height information were available (n = 721 couples). INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Embryologic parameters, clinical pregnancy, and live birth incidence. RESULT(S): The average male BMI among the study population was 27.5 ± 4.8 kg/m(2) (range, 17.3-49.3 kg/m(2)), while the average female BMI (n = 721) was 25.2 ± 5.9 kg/m(2) (range, 16.2-50.7 kg/m(2)). Neither male nor female overweight (25-29.9 kg/m(2)), class I obese (30-34.9 kg/m(2)), or class II/III obese (≥35 kg/m(2)) status was significantly associated with fertilization rate, embryo score, or incidence of pregnancy or live birth compared with normal weight (18.5-24.9 kg/m(2)) status after adjusting for male and female age, partner BMI, and parity. Similar null findings were found between combined couple BMI categories and IVF success. CONCLUSION(S): Our findings support the notion that weight status does not influence fecundity among couples undergoing infertility treatment. Given the limited and conflicting research on BMI and pregnancy success among IVF couples, further research augmented to include other adiposity measures is needed.
Favaro C et al., 2021·J Womens Health (Larchmt)·Free full text on PubMed Central
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. 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. 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. 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.
Lifestyle and Environment › Nutrition and Metabolic Health › Body Weight and Composition
Lauren A Wise, Kenneth J Rothman, Ellen M Mikkelsen, Henrik Toft Sørensen, Elizabeth E Hatch
L Wise, Ken Rothman, K Rothman, E Mikkelsen, H Sørensen, Liz Hatch, Beth Hatch, Betsy Hatch, E Hatch
PMID 19828554 19828554 DOI 10.1093/humrep/dep360 10.1093/humrep/dep360 Wise et al. 2009, Wise 2009
Cite this article
Wise, L. A., Rothman, K. J., Mikkelsen, E. M., Sørensen, H. T., Riis, A., & Hatch, E. E. (2010). An internet-based prospective study of body size and time-to-pregnancy. Human reproduction (Oxford, England), 25(1), 253-264. https://doi.org/10.1093/humrep/dep360
Wise LA, Rothman KJ, Mikkelsen EM, Sørensen HT, Riis A, Hatch EE. An internet-based prospective study of body size and time-to-pregnancy. Hum Reprod. 2010;25(1):253-264. doi:10.1093/humrep/dep360
Wise, L. A., et al. "An internet-based prospective study of body size and time-to-pregnancy." Human reproduction (Oxford, England), vol. 25, no. 1, 2010, pp. 253-264.
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