ORIGINAL ARTICLE: ENVIRONMENT AND EPIDEMIOLOGY

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a
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a,b
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Q9 Craig J. McKinnon, M.P.H., Elizabeth E. Hatch, Ph.D., Kenneth J. Rothman, Dr.P.H.,
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Ellen M. Mikkelsen, Ph.D.,c Amelia K. Wesselink, M.P.H.,a Kristen A. Hahn, Ph.D.,a and Lauren A. Wise, Sc.D.a,d
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a
Department of Epidemiology and d Slone Epidemiology Center, Boston University School of Public Health, Boston,
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Massachusetts; b RTI Health Solutions, Research Triangle Park, Durham, North Carolina; and c Department of Clinical
17 Q1 Epidemiology, Aarhus University Hospital, Aarhus, Denmark
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Objective: To evaluate the association between adiposity, physical activity (PA), and fecundability.
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Design: Prospective cohort study.
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Setting: Not applicable.
Patient(s): A total of 2,062 female pregnancy planners from the United States and Canada who were enrolled during the preconception
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period.
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Intervention(s): None.
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Main Outcome Measure(s): Self-reported pregnancy. Fecundability ratios (FRs) and 95% condence intervals (CIs) were estimated us27
ing proportional probabilities models that adjusted for potential confounders.
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Result(s): Relative to body mass index (BMI) 18.524 kg/m2, FRs for BMI <18.5, 2529, 3034, 3539, 4044, and R45 kg/m2 were
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1.05 (95% CI 0.761.46), 1.01 (95% CI 0.891.15), 0.98 (95% CI 0.821.18), 0.78 (95% CI 0.601.02), 0.61 (95% CI 0.420.88), and 0.42
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(95% CI 0.230.76), respectively. Reduced fecundability was observed among women with the largest waist-to-hip ratios (R0.85 vs.
31 Q2 <0.75; FR 0.87, 95% CI 0.741.01) and waist circumferences (R36 vs. <26 inches; FR 0.80, 95% CI 0.591.01). Tendency to
gain weight in the chest/shoulders (FR 0.63, 95% CI 0.361.08) and waist/stomach (FR 0.90, 95% CI 0.791.02), relative to
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hips/thighs, was associated with lower fecundability. Moderate PA was associated with increased fecundability (R5 vs. <1 h/wk;
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FR 1.26, 95% CI 0.961.65), but there was no dose-response relation. Among overweight/obese women (BMI R25 kg/m2),
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fecundability was 27% higher for vigorous PA of R5 versus <1 h/wk (95% CI 1.021.57).
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Conclusion(s): Various measures of overall and central adiposity were associated with decreased fertility among pregnancy planners.
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Vigorous PA was associated with improved fertility among overweight and obese women only;
37
Use your smartphone
moderate PA was associated with improved fertility among all women. (Fertil Steril 2016;-:
to scan this QR code
--.
2016 by American Society for Reproductive Medicine.)
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and connect to the
Key Words: Fecundability, obesity, physical activity, preconception cohort, time-to-pregnancy
39
discussion forum for
this article now.*
40
Discuss: You can discuss this article with its authors and with other ASRM members at http://
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fertstertforum.com/mckinnonc-bmi-physical-activity-fecundability/
* Download a free QR code scanner by searching for QR
scanner in your smartphones app store or app marketplace.
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he prevalence of overweight and
obese (1, 2). Also rising in these
absolute body fat, have been
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obesity has been rising steadily
populations is the prevalence of
associated with delayed fecundability
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in the United States and Canada,
impaired fecundity (3). Extremes of
in several studies of women, with
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with >1/3 of adults now classied as
body mass index (BMI), a measure of
evidence of a deleterious effect in
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underweight and obese populations
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(411). Underweight may reduce
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Received December 14, 2015; revised April 6, 2016; accepted April 7, 2016.
C.J.M. has nothing to disclose. E.E.H. has nothing to disclose. K.J.R. has nothing to disclose. E.M.M. has
fertility through increased FSH levels
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nothing to disclose. A.K.W. was funded in part by the Boston University Reproductive, Perinatal
(12), secondary amenorrhea (13), and
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and Pediatric Epidemiology training grant (National Institute of Child Health and Human
shortened luteal phase (13). Obesity
Development T32 HD052458). K.A.H. has nothing to disclose. L.A.W. has nothing to disclose.
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Supported by National Institute of Child Health and Human Development (grant R21HD072326).
may decrease fertility through
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Reprint requests: Craig J. McKinnon, M.P.H., Department of Epidemiology, Boston University School
anovulation (1416) and biochemical
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of Public Health, 715 Albany Street, Boston, Massachusetts 02118 (E-mail: craigm@bu.edu).
alterations in the preovulatory
57
Fertility and Sterility Vol. -, No. -, - 2016 0015-0282/$36.00
follicular
environment
(17).
58
Copyright 2016 American Society for Reproductive Medicine, Published by Elsevier Inc.
Underweight and overweight factors
http://dx.doi.org/10.1016/j.fertnstert.2016.04.011
59

Body mass index, physical activity

and fecundability in a North
American preconception
cohort study

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ORIGINAL ARTICLE: ENVIRONMENT AND EPIDEMIOLOGY

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are associated with lower follicular phase E2 levels (18).

Studies have been inconsistent regarding the extent to
which female fecundity is inuenced by central adiposity,
as measured by waist circumference (WC) or waist-to-hip ratio (WHR) (6,1922).
A related factor, physical activity (PA), has thus far
failed to yield consistent results across epidemiologic studies
of infertility (15, 23). Research on competitive female
athletes has identied several factors that might contribute
to a lengthened time to pregnancy (TTP), including
increased risks of oligomenorrhea and amenhorrhea
(2426). Higher levels of PA have also been associated
with increased menstrual cycle length (27), increased
follicular phase length (28), and decreased luteal phase
length (26). Most studies have been based on fertility
clinic populations (29, 30) or have been limited to cases
of ovulatory infertility. Of the four investigations (15, 23,
31, 32) conducted in the general population, the two
studies (15, 23) of ovulatory infertility found that higher
levels of vigorous PA were associated with a decreased
risk of ovulatory infertility. A third report (31), based on a
population-based prospective cohort study of Norwegian
women, found an increased risk of infertility (all types)
among women reporting the highest levels of PA intensity
and frequency. A fourth study (32) in a Danish prospective
cohort of pregnancy planners found that the association between vigorous PA and fecundability varied by BMI.
Whereas vigorous PA was associated with reduced fecundability among lean women (BMI <25 kg/m2), vigorous PA
was associated with increased fecundability among overweight/obese women (BMI R25 kg/m2). Moderate PA was
associated with a small increase in fecundability among
all women.
We prospectively examined the association of body
size and PA with fecundability among female pregnancy
planners enrolled in a North American preconception
cohort study. To address existing gaps in the literature,
we examined additional measures of central adiposity
and body fat distribution, including WC and WHR, as
well as adult weight gain. We further assessed effect measure modication between BMI and PA on the association
with fecundability.

MATERIALS AND METHODS

Study Population
Pregnancy Study Online (PRESTO) is an Internet-based preconception cohort study of pregnancy planners from the
United States or Canada. The study methodology is
described in detail elsewhere (33). Briey, enrolment and
data collection began July 1, 2013 and was accomplished
with the study's website. Eligible women were aged
2145 years, not using contraception or fertility treatments,
in a stable relationship with a male partner, planning a
pregnancy, and not currently pregnant. There were no restrictions for male partners other than an age of
>21 years and that their female partner was enrolled. The
ethical review board of Boston University Medical Center

approved the study protocol and all participants provided

informed consent before participation.

Study Procedures
Female participants completed an online baseline questionnaire that gathered information on demographics, medical
and reproductive history, and lifestyle habits. Female participants also completed online follow-up questionnaires every
8 weeks for >12 months or until reported conception.
Follow-up questionnaires updated information on pregnancy status and exposures that change over time. More
than 80% of women who completed the baseline questionnaire completed at least one follow-up questionnaire (33).
Male participants were invited by their female partners to
complete an optional one-time baseline questionnaire about
their health history.

Exclusions
During 27 months of recruitment (20132016), 2,990 women
enrolled in PRESTO. We excluded women from this analysis
who had been trying to conceive for >6 months before study
entry (n 320), did not complete any follow-up questionnaires (n 506), or had insufcient or implausible information about the date of baseline last menstrual period (LMP)
or rst pregnancy attempt (n 102), leaving 2,062 women
for analysis.

Assessment of Exposure Characteristics

Exposures of interest were ascertained on the female baseline
questionnaire, including height (in inches), weight (in Q3
pounds), WC (in inches), hip circumference (in inches), weight
(in pounds) at age 17 years, and typical weight gain location.
For WC and hip circumference, women were shown a diagram
and asked to measure their waist at the level of navel and to
measure the largest circumference around the hips (including
buttocks). Participants were asked whether they had used a
exible measuring tape or a string to take these measurements (yes vs. no). A measure of weight change since age
17 years (in pounds) was calculated by subtracting the reported weight at age 17 years from a participant's current
weight. This was then categorized into lost weight, and 09,
1019, 2029, 3039 and >40 lb gained.
The PA levels were calculated by asking participants to
report the average number of hours per week during the
past year that they spent performing the following activities;
walking for exercise; walking for transportation; walking at
work; bicycling or stationary bike; jogging/running; lap
swimming; playing tennis and racquetball; performing aerobic exercise (including elliptical machines, aerobics and
dancing); weight training or resistance exercise (including
free weights and weight machines); gardening, mowing and
planting; and yoga, meditation and other stress-reduction activities. Women were asked to report their average hours per
week for each activity using the following categories: none,
<1, 1, 2, 34, 56, and R7 h/wk. The average number of
hours per day a participant spent sitting for entertainment
(including watching television or videos) or work-related
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Fertility and Sterility

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reasons (including driving, working at a computer, or reading)

during the past year was also ascertained using the same
categories.
With these data we calculated BMI (kg/m2), WHR, as well
as composite measures of physical activities and time spent
sitting. To calculate metabolic equivalent (MET) hours per
week, the average number of hours per week spent participating in various activities were multiplied by METs estimated
from the Compendium of Physical Activities (34). The values
for the various activities were as follows: 3.8 METs for
walking for exercise, 2.5 METs for walking for transportation,
2.0 METs for walking at work, 7.5 METs for bicycling, 7.0
METs for jogging, swimming, or racquetball-like activities,
6.5 METs for aerobic exercise, 4.5 METs for weight training/
resistance exercise, 2.5 METs for gardening activities, and
2.5 METs for yoga. Vigorous PA was dened as biking,
jogging, swimming, racquetball, aerobic activities, and
weight training/resistance exercise. Moderate PA was dened
as walking (all types), gardening activities, and yoga.

Assessment of Covariates
On the female baseline questionnaire, women reported data
on age, race/ethnicity, education, household income, parity,
smoking history, alcohol intake, frequency of sexual intercourse, methods to improve chances of conception (e.g.,
monitoring of cervical mucus, charting menstrual cycles,
and basal body temperature), last method of contraception,
partner age and partner height and weight. We also collected
data on male height and weight from the male baseline questionnaire, which, if available, were prioritized versus data
provided by the female partner.

Assessment of Pregnancy and Cycles at Risk

Our outcome of interest was fecundability as measured by
TTP, derived using data from baseline and follow-up questionnaires. We calculated total cycles at risk from the reported
number of cycles trying to conceive at study entry, date of
LMP before enrolment, usual cycle length, and LMP date on
each follow-up questionnaire. Participants contributed cycles
to the analysis from the time of enrolment until reported pregnancy, initiation of fertility treatment, loss to follow-up, or 12
cycles, whichever came rst.

Data Analysis
We used proportional probabilities models to estimate the fecundability ratio (FR), the average per-cycle probability of
conception, and 95% condence interval (CI) for each level
of the exposure variable relative to the referent level. When
possible, we categorized exposure variables using clinically
meaningful cut points (35) (e.g., World Health Organization
standards for BMI); otherwise, we classied women according
to the distribution of the exposure variable in the cohort. A FR
<1 indicates that an exposure is related to a decrease in
fecundability.
We selected potential confounders a priori from the literature as well as by using directed acyclic graphs. We
controlled for female age (<25, 2529, 3034, R35 years),

race/ethnicity (white/non-Hispanic, non-white or Hispanic),

education (high school, some college, completed college,
graduate school), smoking history (never smoker, former
smoker, current smoker), intercourse frequency (<1, 1, 23,
R4 times/wk), last method of contraception (hormonal,
nonhormonal), marital status (married to partner, not married
to partner), income (<$50, $5099, $100149, R$150K),
parity (yes, no), alcohol consumption (0, <1, R1 drinks/d),
and male partner BMI (<18.5, 18.524, 2529, R30 kg/m2).
Vigorous PA and moderate PA were mutually adjusted; analyses of METs were not further adjusted for either type of PA.
The PA models were adjusted for BMI, and the BMI models
were adjusted for PA.
We performed stratied analyses to evaluate whether
BMI (<25 vs. R25 kg/m2) modied the associations between
PA and fecundability, in an effort to replicate the results from
a previous study (32). We also assessed whether the associations of fecundability with body size and PA were uniform
across levels of attempt time at study entry (<3 vs. R3 cycles)
in an effort to address selection bias and exposure misclassication resulting from lifestyle changes made due to difculty conceiving.
The percentage of missing data ranged from 0 (age) to
38.1% (WC). We used PROC MI, with 144 variables in the
model, to multiply impute missing values for exposures and
covariates by creating ve imputed datasets. We used PROC
MIANALYZE to combine coefcient and SE estimates from
the ve datasets (36).

RESULTS
There were 2,062 women in the study contributing 9,314 cycles and 1,274 pregnancies. The mean age of cohort participants was 30.5 years (range, 2144 years). After 6 and 12
cycles of pregnancy attempts, 52.3% and 76.1% of women reported a pregnancy, respectively. Baseline characteristics according to female BMI and PA are presented in Table 1. The
BMI was positively associated with WHR, WC, partner BMI,
weight change since age 17 years, and pack-years of smoking,
and inversely associated with education, income, total MET
hours per week, and alcoholic drinks per week. Vigorous PA
was positively associated with hormonal contraceptive use
and alcohol consumption and inversely associated with frequency of intercourse, WHR, WC, and partner BMI.
Table 2 presents the FRs for measures of body size and
physical activity. The FRs associated with female BMI of
<18.5, 2529, 3034, 3539, 4044, and R45 kg/m2 were
1.05 (95% CI 0.761.46), 1.01 (95% CI 0.891.15), 0.98
(95% CI 0.821.18), 0.78 (95% CI 0.601.02), 0.61 (95% CI
0.420.88), and 0.42 (95% CI 0.230.76), respectively,
compared with BMI of 18.524 kg/m2. No single covariate accounted for the difference between the crude and adjusted
models for BMI results. Omission of possible causal intermediates (e.g., intercourse frequency) from the multivariable
model made little difference in the FRs for BMI. Measures of
central adiposity, WC, and WHR, were also inversely associated with fecundability and these associations persisted after
further control for BMI. The FR was 0.80 (95% CI 0.591.09)
comparing WC R36 inches with <26 inches, after adjusting

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Baseline characteristics of 2,062 women according to female body mass index (BMI) and physical activity, PRESTO, 20132016.
Body mass index (kg/m2)

Vigorous activity (h/wk)

Characteristic
Age at baseline, y (mean)
Partner age, y (mean)
Total MET-h/wk (mean)
Sitting R7 h/d (%)
Waist-to-hip ratio (mean)
Waist circumference, inches (mean)
Weight change since age 17 y, lbs (mean)
Female BMI, kg/m2 (mean)
Partner BMI, kg/m2 (mean)
Education, y (mean)
Do something to improve chances of conception (%)
Intercourse <1 time per wk (%)
Last used hormone contraceptive (%)
Last used barrier contraceptive (%)
White, non-Hispanic (%)
Income <$50,000 (%)
Alcohol, drinks/wk (mean)
Pack-years among ever smokers (mean)
Attempt time at study entry, mo (mean)

<1
(n [ 655)

12
(n [ 503)

34
(n [ 388)

56
(n [ 226)

7
(n [ 290)

<18.5
(n [ 43)

18.524
(n [ 1,067)

2529
(n [ 486)

3034
(n [ 236)

35
(n [ 230)

29.7
31.9
17.3
55.3
2.8
33.9
30.7
28.1
28.9
15.6
76.1
23.1
37.7
42.8
84.9
20.1
2.6
4.2
2.2

30.0
32.0
29.4
54.2
2.6
32.4
24.3
26.6
28.4
16.1
73.5
21.1
37.3
39.7
86.2
15.6
3.7
3.3
2.0

30.4
32.2
44.3
57.9
2.5
31.1
16.5
24.9
27.0
16.2
73.6
21.6
36.9
42.9
85.9
13.9
3.6
3.5
1.9

30.0
31.5
58.3
56.1
2.5
30.9
16.4
25.2
27.3
16.2
77.5
13.3
42.1
43.7
88.0
12.2
3.8
2.8
2.2

30.0
32.2
89.6
52.3
2.7
30.9
18.4
25.1
26.9
16.0
73.3
15.1
45.1
31.3
85.7
17.7
4.4
2.9
2.2

28.8
32.1
40.8
58.2
2.1
25.9
0.1

25.5
16.3
67.3
32.3
45.0
39.5
84.3
22.5
3.9
2.7
1.6

30.0
32.1
43.1
53.8
2.3
28.7
9.7

26.3
16.2
74.7
18.0
39.3
38.8
87.3
14.1
3.7
3.3
2.0

30.1
31.6
39.1
54.9
2.8
33.1
24.1

28.6
16.0
77.1
21.0
41.3
38.9
85.3
14.9
3.8
3.5
2.1

30.2
32.3
34.6
54.5
3.1
37.3
44.0

29.7
15.7
76.3
22.5
33.0
51.4
81.0
18.3
3.0
4.1
2.4

29.6
31.8
32.5
62.8
3.3
42.7
65.1

33.1
15.3
71.6
26.5
38.9
41.3
85.9
30.8
1.9
4.1
2.4

Note: All characteristics are age standardized to the cohort at baseline, with the exception of age. PRESTO Pregnancy Study Online.
McKinnon. BMI, PA and fecundability. Fertil Steril 2016.

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TABLE 1

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Fertility and Sterility

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TABLE 2
Associations of fecundability with physical activity and BMI, PRESTO, 20132016.
Exposure

No. of pregnancies

Anthropometric measures
Body mass index (kg/m2)b
<18.5
31
18.524
694
2529
310
3034
136
3539
62
4044
30
R45
11
b,c
Waist-to-hip ratio
<0.75
330
0.750.79
317
0.800.84
255
R0.85
372
Waist circumference (inches)b,c
<26
106
2630
555
3135
354
R36
259
Weight change since age 17 (lbs)b,c
Lost weight
177
Gain 09
244
Gain 1019
270
Gain 2029
201
Gain 3039
140
Gain R40
236
Weight gain locationb,c
No gain
44
Chest/shoulder
12
Waist/stomach
505
Hips/thighs
381
Equally all over
315
Other
17
Physical activity measures
c
Vigorous PA (h/wk)
<1
372
12
316
34
256
R5
330
Moderate PA (h/wk)c
<1
53
12
253
34
286
R5
682
Total PA (MET-h/wk)c
010
125
1119
161
2029
192
3039
208
4049
164
5059
134
R60
281
Sitting (h/d)b,c
<3
61
34
272
56
244
R7
697

No. of cycles

Unadjusted FR (95% CI)

Adjusteda FR (95% CI)

190
4,523
2,182
1,078
688
416
237

0.97 (0.701.34)
1.00 (Reference)
0.94 (0.841.07)
0.87 (0.741.03)
0.67 (0.520.85)
0.51 (0.360.72)
0.34 (0.190.60)

1.05 (0.761.46)
1.00 (Reference)
1.01 (0.891.15)
0.98 (0.821.18)
0.78 (0.601.02)
0.61 (0.420.88)
0.42 (0.230.76)

2,055
2,001
1,991
3,267

1.00 (Reference)
0.98 (0.841.14)
0.90 (0.761.06)
0.76 (0.650.88)

1.00 (Reference)
1.04 (0.891.21)
0.94 (0.791.11)
0.87 (0.741.01)

734
3,558
2,366
2,656

1.00 (Reference)
1.02 (0.841.25)
1.00 (0.811.24)
0.67 (0.530.85)

1.00 (Reference)
1.04 (0.851.27)
1.02 (0.811.29)
0.80 (0.591.09)

1,069
1,622
1,681
1,366
1,103
2,431

1.09 (0.911.29)
1.00 (Reference)
1.08 (0.921.26)
1.02 (0.861.21)
0.93 (0.771.12)
0.70 (0.590.82)

1.11 (0.931.32)
1.00 (Reference)
1.14 (0.971.34)
1.09 (0.911.30)
1.03 (0.831.27)
0.90 (0.721.12)

280
122
3,881
2,286
2,665
80

0.93 (0.701.23)
0.63 (0.371.07)
0.82 (0.730.92)
1.00 (Reference)
0.75 (0.660.86)
1.21 (0.791.84)

0.93 (0.691.24)
0.63 (0.361.08)
0.90 (0.791.02)
1.00 (Reference)
0.82 (0.710.94)
1.20 (0.781.84)

3,135
2,265
1,690
2,224

1.00 (Reference)
1.13 (0.981.30)
1.23 (1.071.43)
1.22 (1.061.40)

1.00 (Reference)
1.04 (0.911.20)
1.16 (1.001.35)
1.11 (0.961.28)

536
1,771
2,124
4,883

1.00 (Reference)
1.44 (1.081.91)
1.33 (1.011.76)
1.40 (1.071.84)

1.00 (Reference)
1.29 (0.971.73)
1.16 (0.871.54)
1.26 (0.961.65)

1,039
1,287
1,508
1,447
1,129
818
1,998

1.00 (Reference)
1.01 (0.821.25)
1.03 (0.841.27)
1.16 (0.941.44)
1.22 (0.991.51)
1.28 (1.021.60)
1.15 (0.951.40)

1.00 (Reference)
0.97 (0.781.20)
0.95 (0.781.17)
1.07 (0.861.32)
1.13 (0.911.40)
1.23 (0.991.54)
1.06 (0.871.28)

581
2,009
1,514
5,210

0.81 (0.621.04)
1.00 (Reference)
1.16 (0.991.35)
0.98 (0.861.11)

0.78 (0.611.02)
1.00 (Reference)
1.17 (1.001.37)
1.03 (0.901.17)

Note: BMI body mass index; CI condence interval; FR fecundability ratio; PA physical activity; PRESTO Pregnancy Study Online.
a
Adjusted for age, parity, intercourse frequency, education, race/ethnicity, household income, marital status, last method of contraception, alcohol consumption, smoking and partner BMI.
b
Model further adjusted for PA.
c
Model further adjusted for BMI.
McKinnon. BMI, PA and fecundability. Fertil Steril 2016.

for BMI. Similarly, the FR comparing WHR R0.85 with <0.75

was 0.87 (95% CI 0.741.01), after adjusting for BMI. Reduced
fecundability was observed only among women gaining R40
pounds since age 17 years (FR 0.89, 95% CI 0.721.11).

We further examined the possibility of a linear relationship between BMI and fecundability. We added knot points
at the clinically meaningful BMI cut points of 25, 30, and
35 kg/m2. Figure 1 conrms our ndings from the categorical

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534
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541
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569
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574
575
576
577
578
579
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582
583
584
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589
590

ORIGINAL ARTICLE: ENVIRONMENT AND EPIDEMIOLOGY

591
FIGURE 1
592
593
594
595
596
597
598
599
600
601
602
603
604
605
606
607
608
609
610
611
Linear spline for body mass index (BMI) and fecundability ratio.
612
Association between BMI and fecundability, tted by restricted
613
cubic splines using three knots located at 25, 30, and 35 kg/m2.
614
Reference level for fecundability ratio is 22 kg/m2. The curve is
adjusted for vigorous physical activity (PA), moderate PA, age,
615
parity, intercourse frequency, education, race/ethnicity, marital
616
status, alcohol intake, partner BMI, income, last method of
617
contraception, and smoking status. Solid line represents
618
fecundability ratio and dotted lines denote 95% condence bounds.
619
McKinnon. BMI, PA and fecundability. Fertil Steril 2016.
620
621
622
BMI analysis, showing a reduction in fecundability starting
623
around BMI of 30 kg/m2, and becoming stronger as BMI
624
increases.
625
We observed slightly lower fecundability among women
626
who reported a tendency for weight gain primarily in the
627
waist and stomach (FR 0.90, 95% CI 0.791.02), in the chest
628
and shoulders (FR 0.63, 95% CI 0.361.08), or equally all
629
over (FR 0.82, 95% CI 0.710.94), relative to weight gain
630 Q4 primarily in the hips and thighs.
631
Moderate PA was associated with a modest increase in fe632
cundability, but there was little evidence of a dose-response
633
relation (Table 2). The FRs for moderate PA of 12, 34, and
634
R5 hours per week were 1.29 (95% CI 0.971.73), 1.16
635
(95% CI 0.871.54), and 1.26 (95% CI 0.961.65), respectively,
636
compared with <1 hour per week. Further splitting of the
637
highest moderate PA category into two yielded similar results
638
(FR 1.28, 95% CI 0.961.73 and FR 1.25, 95% CI 0.95
639
1.64 for 56 and R7 hours per week, respectively). Vigorous
640
PA showed weaker associations fecundability, with FRs
641
ranging from 1.041.16. Examining total METs from all PA
642
activities combined yielded no substantial association be643
tween PA and fecundability. Time spent sitting showed little
644
association with fecundability.
645
Among women with a BMI of R25 kg/m2, the FR for
646
vigorous PA of R5 relative to <1 hour per week was 1.27
647
(95% CI 1.021.67; Table 3). Among women with a BMI of
648
<25 kg/m2, there was no material relation between vigorous
649
PA and fecundability.

Stratifying by the time a couple had been attempting to

conceive at study entry had little effect on the association between BMI and fecundability, with the exception of the BMI
<18.5 category, for which we had small numbers of participants (n 12). Among those who had been attempting to
conceive for <3 cycles at study entry, vigorous PA was
weakly positively associated with fecundability (FRs ranging
from 1.111.28), whereas among those who had been trying
for R3 cycles, vigorous PA had the opposite effect (FRs
ranging from 0.880.95) (Table 4).
Q5

DISCUSSION
In this study of North American pregnancy planners, we
found that high levels of overall and central adiposity were
associated with decreased fecundability in women. These associations persisted after adjusting for a variety of potential
confounders, and with mutual adjustment for central and
overall obesity measures. We found a nonlinear positive association between moderate PA and fecundability. Vigorous PA
was associated with increased fecundability among overweight/obese women, but not normal weight women.
Our results are consistent with previous studies (411,
3537) showing that female obesity is associated
with delayed fecundability. Although several other studies
(46,8) found that being underweight was also associated
with decreased fecundability, we did not nd evidence of
decreased fecundability among underweight women. The
number of women in our study classied with a BMI <18.5
was small (n 43). Adult weight gain since age 17 years in
excess of 40 pounds was associated with reduced
fecundability in our cohort. This agrees with two previous
studies (22, 38), both of which found that excess adult
weight gain was associated with longer TTP.
Our nding of a small positive association between moderate PA and fecundability agrees with previous studies
(30, 32). Likewise, our nding of vigorous PA and improved
fecundability among overweight/obese women has been
shown in other populations (32, 39). We found little
evidence for an association of fecundability with vigorous
PA (among normal weight women), total MET-hours per
week, or hours spent sitting. Previous studies (15, 23, 31) of
vigorous PA have been mixed. To our knowledge, there are
no previous studies investigating the inuence of sedentary
behaviors on female fecundity.
Consistent with most (6,1921), but not all (22), previous
studies of central adiposity and fecundity, we found that
women with larger WC and WHR experienced decreased
fecundability. Our results for location of weight gain agreed
with results for the more formal measures of central
adiposity, indicating that weight gained in the waist/
stomach and chest/shoulder areas was associated with lower
fertility relative to weight gain in the hips/thighs area.
Study limitations include the potential for exposure
misclassication. Our measures of adiposity and PA were
self-reported by the participant. The PA measurements were
not validated according to activity type, frequency, or intensity. Although BMI has been shown to have excellent
reliability when compared with technician measurements
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650
651
652
653
654
655
656
657
658
659
660
661
662
663
664
665
666
667
668
669
670
671
672
673
674
675
676
677
678
679
680
681
682
683
684
685
686
687
688
689
690
691
692
693
694
695
696
697
698
699
700
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703
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705
706
707
708

Fertility and Sterility

709
710
711
712
713
714
715
716
717
718
719
720
721
722
723
724
725
726
727
728
729
730
731
732
733
734
735
736
737
738
739
740
741
742
743
744
745
746
747
748
749
750
751
752
753
754
755
756
757
758
759
760
761
762
763
764
765
766
767

TABLE 3
Selected associations with fecundability, stratied by body mass index and attempt time at study entry.
No. of
cycles

BMIa <25 kg/m2

(95% CI)
(n [ 1,110)

No. of
pregnancies

No. of
cycles

BMIa 25 kg/m2
(95% CI) (n [ 952)

179
172
171
203

1,235
1,124
1,004
1,350

1.00 (Reference)
1.01 (0.831.23)
1.16 (0.961.41)
1.02 (0.841.24)

193
144
85
127

1,900
1,141
686
874

1.00 (Reference)
1.11 (0.901.36)
1.13 (0.881.45)
1.27 (1.021.57)

25
140
167
393

220
827
1,195
2,471

1.00 (Reference)
1.43 (0.942.16)
1.16 (0.781.73)
1.34 (0.901.98)

28
113
119
289

316
944
929
2,412

1.00 (Reference)
1.16 (0.761.79)
1.22 (0.811.83)
1.19 (0.801.77)

No. of
pregnancies

No. of
cycles

Attempt at entry
<3 cyclesa (95% CI)
(n [ 1,364)

No. of
pregnancies

No. of
cycles

Attempt at entry3
cyclesa (95% CI)
(n [ 698)

246
235
202
228

2,105
1,618
1,193
1,374

1.00 (Reference)
1.11 (0.941.31)
1.28 (1.081.53)
1.18 (0.991.41)

126
81
54
102

1,030
647
497
850

1.00 (Reference)
0.94 (0.721.23)
0.88 (0.651.20)
0.95 (0.741.23)

22
517
223
83
66

146
3,179
1,488
613
864

0.90 (0.611.33)
1.00 (Reference)
1.03 (0.891.20)
1.00 (0.801.25)
0.65 (0.490.85)

9
177
87
53
37

44
1,344
694
465
477

2.21 (1.244.04)
1.00 (Reference)
0.94 (0.731.20)
0.95 (0.701.30)
0.73 (0.501.06)

No. of
pregnancies

Exposure

Vigorous PA (h/wk)b
<1
12
34
R5
Moderate PA (h/wk)c
<1
12
34
R5

Exposure
Vigorous PAd
<1
12
34
R5
BMIb,c
<18.5
18.524
2529
3034
R35

Note: BMI body mass index; CI condence interval; PA physical activity.

a
Adjusted for age, parity, intercourse frequency, education, race/ethnicity, household income, last method of contraception, alcohol consumption, smoking, and partner BMI.
b
Model further adjusted for moderate PA.
c
Model further adjusted for vigorous PA.
d
Model further adjusted for BMI.
McKinnon. BMI, PA and fecundability. Fertil Steril 2016.

(22, 40), it is quite likely that other anthropometric

measurements (e.g., WC and hip circumference) and PA
levels were misclassied. Given the prospective nature of
our study design, we would expect the misclassication to
be nondifferential, with the highest category biased toward
the null. Participants who had already been attempting to
conceive for several months at study entry might have
adjusted their behaviors or had differential recall of their
behaviors. The observed differences in association between
vigorous PA and fecundability by attempt time at study
entry supports this hypothesis. Conversely, the association
between BMI R35 kg/m2 and fecundability was uniform
across categories of attempt time at study entry, which is
not surprising because BMI tends to remain more stable
during a 6-month interval. Differential recognition of
pregnancy among obese and nonobese women is unlikely
to explain our BMI ndings given recent research showing
no evidence to support this phenomenon (41).
Internet-based recruitment is often mentioned as a criticism of our study design, with the main complaint being
that Internet users and nonusers differ from each other. However, it is unlikely that Internet usage would be both associated with exposure and outcome. In our Danish
preconception study (Snart Gravid), we used data from the
Danish Medical Birth Registry (20082012) to compare six
well-known perinatal associations to our volunteer cohort

(n 4,801) with the total population of singleton live births

in the registry (n 239,791). Despite notable differences in
the prevalence of several demographic and lifestyle covariates
between the study groups, perinatal associations were nearly
identical across the study groups (42). These ndings were
consistent with two other studies that have performed a
similar comparison of their volunteer cohort with the rest of
the country (43, 44).
With regard to generalizability, the high prevalence of
Internet use in the United States and Canada (86%) (4547)
suggests that study participation was available to most
women. Participation in Internet-based prospective cohort
studies does not introduce new concerns about validity
beyond those already present in traditional prospective cohort
studies of volunteers, including clinical trials (4851).
External validity should not be affected by volunteering,
unless summary measures of association are modied by
factors that are distributed differently among the study
subjects than among target populations, thereby affecting
the overall average effect. Within subcategories of these
effect modiers, effects would be the same among the study
population and the source population. Furthermore, unlike
survey research, the ideal target population for
generalization of our data is not the current population of
couples in the countries where the study is conducted, but
rather future couples in these and other countries (52).

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769
770
771
772
773
774
775
776
777
778
779
780
781
782
783
784
785
786
787
788
789
790
791
792
793
794
795
796
797
798
799
800
801
802
803
804
805
806
807
808
809
810
811
812
813
814
815
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818
819
820
821
822
823
824
825
826

ORIGINAL ARTICLE: ENVIRONMENT AND EPIDEMIOLOGY

827
828
829
830
831
832
833
834
835
836
837
838
839
840
841
842
843
844
845
846
847
848
849
850
851
852
853
854
855
856
857
858
859
860
861
862
863
864
865
866
867
868
869
870
871
872
873
874
875
876
877
878 Q6
879
880
881
882
883
884
885

One of the main strengths of PRESTO is that participant

recruitment occurs during the preconception period, thereby
avoiding many of the limitations of retrospective TTP studies,
such as selection bias, recall bias, and loss of accuracy and
precision due to left truncation (5356). Most participants
enrolled at the beginning of their pregnancy attempt, with
68% of the cohort having <3 months of attempt time at
entry into the study. This reduces potential for reverse
causation (i.e., spuriously identifying lifestyle changes made
by subfertile women to improve their fertility as risk
factors). Another strength is the collection of data on
measures of adiposity and body fat distribution not
routinely collected in epidemiologic studies, including WC
and hip circumference and areas of typical weight gain.
This allowed us to look beyond BMI to perform a more
comprehensive examination of the association between
body fat and TTP. Finally, collection of data on a variety of
covariates from both partners, including male partner's
BMI, permitted better control for potential confounding.
In conclusion, in this study, we conrmed previous
research showing an association between overall obesity
and reduced fecundability among women. We also found evidence that central obesity is an important risk factor for
reduced fecundability. The association between PA and fecundability was more complex, with moderate PA being associated with improved fecundability among all women, but
vigorous PA being associated with increased fecundability
among overweight and obese women only.
Acknowledgments: We acknowledge the contributions of
PRESTO participants and staff. We thank Michael Bairos for
his technical support with developing the web-based infrastructure of PRESTO. We are grateful to Drs. Frederic Montoya
and Heather Bromberg for their generous donation of FertilityFriend.com memberships. We thank Alexandra E. Kriss and
Alina Chaiyasarikul for their technical assistance and instrumental support of the study.

2.

3.

4.
5.

6.

7.
8.

10.

11.

12.

13.
14.
15.

16.

17.

18.

19.
20.

21.

22.

23.

24.

REFERENCES
1.

9.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM.
Prevalence of overweight and obesity in the United States, 19992004.
JAMA 2006;295:154955.
Twells LK, Gregory DM, Reddigan J, Midodzi WK. Current and predicted
prevalence of obesity in Canada: a trend analysis. CMAJ Open 2014;2:
E1826.
Chandra A, Martinez GM, Mosher WD, Abma JC, Jones J. Fertility, family
planning, and reproductive health of U.S. women: data from the 2002 National Survey of Family Growth. Vital Health Stat 2005;23:1160.
Hassan MA, Killick SR. Negative lifestyle is associated with a signicant
reduction in fecundity. Fertil Steril 2004;81:38492.
Bolumar F, Olsen J, Rebagliato M, Saez-Lloret I, Bisanti L, the European Study
Group on Infertility and Subfecundity. Body mass index and delayed conception: a European multicenter study on infertility and subfecundity. Am J Epidemiol 2000;151:10729.
Zaadstra BM, Seidell JC, Van Noord PA, te Velde ER, Habbema JD,
Vrieswijk B, et al. Fat and female fecundity: prospective study of effect of
body fat distribution on conception rates. BMJ 1993;306:4847.
Diamanti-Kandarakis E, Bergiele A. The inuence of obesity on hyperandrogenism and infertility in the female. Obes Rev 2001;2:2318.
Gesink Law DC, Maclehose RF, Longnecker MP. Obesity and time to pregnancy. Hum Reprod 2007;22:41420.

25.

26.

27.

28.
29.

30.

31.

Nohr EA, Vaeth M, Rasmussen S, Ramlau-Hansen CH, Olsen J. Waiting time

to pregnancy according to maternal birthweight and prepregnancy BMI.
Hum Reprod 2009;24:22632.
Ramlau-Hansen CH, Thulstrup AM, Nohr EA, Bonde JP, Sorensen TI, Olsen J.
Subfecundity in overweight and obese couples. Hum Reprod 2007;22:
16347.
Q7
Jensen TK, Scheike T, Keiding N, Schaumburg I, Grandjean P. Fecundability
in relation to body mass and menstrual cycle patterns. Epidemiology 1999;
10:4228.
Cramer DW, Barbieri RL, Xu H, Reichardt JKV. Determinants of basal follicle
stimulating hormone levels in premenopausal women. J Clin Endocrinol
Metab 1994;79:11059.
Frisch RE. Body fat, menarche, tness and fertility. Hum Reprod 1987;2:
52133.
Grodstein F, Goldman MB, Cramer DW. Body mass index and ovulatory
infertility. Epidemiology 1994;5:24750.
Rich-Edwards JW, Spiegelman D, Garland M, Hertzmark E, Hunter DJ,
Colditz GA, et al. Physical activity, body mass index, and ovulatory disorder
infertility. Epidemiology 2002;13:18490.
Rich-Edwards JW, Goldman MB, Willett WC, Hunter DJ, Stampfer MJ,
Colditz GA, et al. Adolescent body mass index and infertility caused by
ovulatory disorder. Am J Obstet Gynecol 1994;171:1717.
Robker RL, Akison LK, Bennett BD, Thrupp PN, Chura LR, Russell DL, et al.
Obese women exhibit differences in ovarian metabolites, hormones, and
gene expression compared to moderate weight women. J Clin Endocrinol
Metab 2009;94:53340.
Ziomkiewicz A, Ellison PT, Lipson SF, Thune I, Jasienska G. Body fat, energy
balance and estradiol levels: a study based on hormonal proles from complete menstrual cycles. Hum Reprod 2008;23:255563.
Wise LA, Palmer JR, Rosenberg L. Body size and time-to-pregnancy in black
women. Hum Reprod 2013;28:285664.
Wass P, Waldenstrom U, Rossner S, Hellberg D. An android body fat distribution in females impairs the pregnancy rate of in-vitro fertilization-embryo
transfer. Hum Reprod 1997;12:205760.
Jasienska G, Ziomkiewicz A, Ellison PT, Lipson SF, Thune I. Large breasts and
narrow waists indicate high reproductive potential in women. Proc Biol Sci
2004;271:12137.
Wise LA, Rothman KJ, Mikkelsen EM, Sorensen HT, Riis A, Hatch EE. An
internet-based prospective study of body size and time-to-pregnancy.
Hum Reprod 2010;25:25364.
Chavarro JE, Rich-Edwards JW, Rosner BA, Willett WC. Diet and lifestyle in
the prevention of ovulatory disorder infertility. Obstet Gynecol 2007;110:
10508.
Frisch RE, Gotz-Welbergen AV, McArthur JW, Albright T, Witschi J, Bullen B,
et al. Delayed menarche and amenorrhea of college athletes in relation to
age of onset of training. JAMA 1981;246:155963.
Dadgostar H, Razi M, Aleyasin A, Alenabi T, Dahaghin S. The relation between
athletic sports and prevalence of amenorrhea and oligomenorrhea in Iranian
female athletes. Sports Med Arthrosc Rehabil Ther Technol 2009;1:16.
De Souza MJ, Toombs RJ, Scheid JL, O'Donnell E, West SL, Williams NI. High
prevalence of subtle and severe menstrual disturbances in exercising
women: conrmation using daily hormone measures. Hum Reprod 2010;
25:491503.
Cooper G, Sandler D, Whelan E, Smith K. Association of physical and behavioral characteristics with menstrual cycle patterns in women 2931 years of
age. Epidemiology 1996;7:6248.
Liu Y, Gold EB, Lasley BL, Johnson WO. Factors affecting menstrual cycle
characteristics. Am J Epidemiol 2004;160:13140.
Morris SN, Missmer SA, Cramer DW, Powers RD, McShane PM,
Hornstein MD. Effects of lifetime exercise on the outcome of in vitro fertilization. Obstet Gynecol 2006;108:93845.
Kucuk M, Doymaz F, Urman B. Effect of energy expenditure and physical activity on the outcomes of assisted reproduction treatment. Reprod Biomed
Online 2010;20:2749.
Gudmundsdottir SL, Flanders WD, Augestad LB. Physical activity and
fertility in women: the North-Trndelag Health Study. Hum Reprod
2009;24:3196204.

VOL. - NO. - / - 2016

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Para uso personal exclusivamente. No se permiten otros usos sin autorizacin. Copyright 2016. Elsevier Inc. Todos los derechos reservados.

886
887
888
889
890
891
892
893
894
895
896
897
898
899
900
901
902
903
904
905
906
907
908
909
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913
914
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917
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919
920
921
922
923
924
925
926
927
928
929
930
931
932
933
934
935
936
937
938
939
940
941
942
943
944

Fertility and Sterility

945
946
947
948
949
950
951
952
953
954
955
956
957
958
959
960
961
962
963
964
965
966
967
968
969
970
971
972
973
974
975
976
977
978
979
980
981
982
983
984
985
986
987
988
989
990
991
992
993
994
995
996
997
998
999
1000
1001
1002
1003

32.

33.

34.

35.

36.
37.

38.

39.

40.
41.

42.

43.

Wise LA, Rothman KJ, Mikkelsen EM, Sorensen HT, Riis AH, Hatch EE. A prospective cohort study of physical activity and time to pregnancy. Fertil Steril
2012;97:113642. e14.
Wise LA, Rothman KJ, Mikkelsen EM, Stanford JB, Wesselink AK,
McKinnon C, et al. Design and conduct of an Internet-based preconception
cohort study in North America: pregnancy study online. Paediatr Perinat Epidemiol 2015;29:36071.
Ainsworth BE, Haskell WL, Whitt MC, Irwin ML, Swartz AM,
Strath SJ, et al. Compendium of physical activities: an update of activity codes and MET intensities. Med Sci Sports Exerc 2000;32:
S498504.
WHO Expert Committee. Physical status: the use and interpretation of
anthropometry. Report of a WHO Expert Committee. World Health Organ
Tech Rep Ser 1995;854:1452.
SAS Institute. SAS/Stat 9.3 user's guide. Cary, NC: SAS Institute; 2008.
Wise LA, Palmer JR, Heffner LJ, Rosenberg L. Prepregnancy body size, gestational weight gain, and risk of preterm birth in African-American women.
Epidemiology 2010;21:24352.
Gaskins AJ, Rich-Edwards JW, Missmer SA, Rosner B, Chavarro JE. Association of fecundity with changes in adult female weight. Obstet Gynecol 2015;
126:8508.
Clark AM, Ledger W, Galletly C, Tomlinson L, Blaney F, Wang X, et al.
Weight loss results in signicant improvement in pregnancy and
ovulation rates in anovulatory obese women. Hum Reprod 1995;10:
270512.
Rothman KJ. BMI-related errors in the measurement of obesity. Int J Obes
(Lond) 2008;3(32 Suppl):S569.
Lynch CD, Tumin R, Prasad MR. Association between body mass index and
the timing of pregnancy recognition and entry into prenatal care. Obstet Gynecol 2014;124:9118.
Hatch EE, Hahn KA, Wise LA, Mikkelsen EM, Kumar R, Riis AR, et al. Evaluation of selection bias in an Internet-based study of pregnancy planners.
Epidemiology 2016;27:98104.
Nohr EA, Frydenberg M, Henriksen TB, Olsen J. Does low participation in
cohort studies induce bias? Epidemiology 2006;17:4138.

44.

45.

46.

47.

48.

49.
50.
51.

52.

53.

54.
55.
56.

Nilsen RM, Vollset SE, Gjessing HK, Skjaerven R, Melve KK, Schreuder P, et al.
Self-selection and bias in a large prospective pregnancy cohort in Norway.
Paediatr Perinat Epidemiol 2009;23:597608.
Computer and Internet Access in the United States, 2012. Available at:
http://www.census.gov/hhes/computer/les/2012/Computer_Use_Infographic_
FINAL.pdf. Accessed Febuary 10, 2016.
Q8
Canadian Internet Use Survey, 2012. Available at: http://www.
statcan.gc.ca/daily-quotidien/131126/dq131126d-eng.htm. Accessed Febuary 10, 2016.
Canadian Digital, Social and Mobile Statistics on a Global Scale. Available at:
http://canadiansinternet.com/canadian-digital-social-mobile-statistics-globalscale-2014/; 2014. Accessed Febuary 10, 2016.
Wise LA, Cramer DW, Hornstein MD, Ashby RK, Missmer SA. Physical activity
and semen quality among men attending an infertility clinic. Fertil Steril
2011;95:102530.
Arce JC, De Souza MJ. Exercise and male factor infertility. Sports Med 1993;
15:14669.
Arce JC, De Souza MJ, Pescatello LS, Luciano AA. Subclinical alterations in
hormone and semen prole in athletes. Fertil Steril 1993;59:398404.
De Souza MJ, Arce JC, Pescatello LS, Scherzer HS, Luciano AA. Gonadal hormones and semen quality in male runners. A volume threshold effect of
endurance training. Int J Sports Med 1994;15:38391.
Rothman K, Hatch E, Poole C, Wise L, Gallacher J, Lash T, et al. Comment on
Perils and Potentials of Self-Selected Entry to Epidemiological Studies and
Surveys. J Roy Stat Soc 2016:3556. Series A (Statistics in Society).
Schisterman EF, Cole SR, Ye A, Platt RW. Accuracy loss due to selection bias
in cohort studies with left truncation. Paediatr Perinat Epidemiol 2013;27:
491502.
Joffe M, Key J, Best N, Keiding N, Scheike T, Jensen TK. Studying time to pregnancy by use of a retrospective design. Am J Epidemiol 2005;162:11524.
Weinberg CR, Baird DD, Wilcox AJ. Sources of bias in studies of time to pregnancy. Stat Med 1994;13:67181.
Baird DD, Weinberg CR, Schwingl P, Wilcox AJ. Selection bias associated
with contraceptive practice in time-to-pregnancy studies. Ann N Y Acad
Sci 1994;709:15664.

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