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\begin{document}

\title{Association of chronotype and depressive symptoms in Chinese infertile
population undergoing assisted reproductive technology}



\author[1]{Danni Wang}%
\author[1]{Fei Jiang}%
\author[1]{Mengli Zhu}%
\author[1]{Yuedi Jia}%
\author[1]{Xiaohuan Song}%
\author[2]{Wang Jieyu}%
\author[2]{Qianhua Xu}%
\author[2]{Guiying Luo}%
\affil[1]{Anhui Medical University School of Public Health}%
\affil[2]{First Affiliated Hospital of Anhui Medical University Reproductive Medicine Center}%


\vspace{-1em}



  
  \date{June 14, 2024}


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\selectlanguage{english}
\begin{abstract}
\textbf{Objective:} To assess the association between chronotype and
depressive symptoms in an infertile population undergoing assisted
reproductive technology. \textbf{Design:} Cross-sectional study.
\textbf{Setting:} The First Affiliated Hospital of Anhui Medical
University Reproductive Medicine Center in Hefei, China.
\textbf{Population:} 1022 infertile patients who sought assisted
reproductive technology at the Center between August and October 2022,
were assessed for inclusion in this study. \textbf{Methods:} On the day
of ovulation injection, we collected socio-demographics by inviting
infertile patients to complete questionnaires and assessed the subjects'
chronotypes through the Morning and Evening Questionnaire-5 Items
(MEQ-5). \textbf{Main Outcome Measures:} Depressive symptoms, assessed
with validated Patient Health Questionnaire-9 (PHQ-9) and expressed as
PHQ-9 scores. \textbf{Results:} Overall, 9\%, 68\%, and 22\% of
participants were categorized as evening, neutral, and morning
chronotypes, respectively. There were significant differences between
chronotype on levels of depressive symptoms, subjects with morning
chronotype (odds ratios = 0.32, 95\% confidence intervals: 0.18-0.57)
and neutral chronotype (odds ratios = 0.47, 95\% confidence intervals:
0.28-0.77) had lower odds of depressive status, compared to those with
evening chronotype, but no partner effect of chronotype was found (
\emph{p} \textgreater{}0.05, respectively). \textbf{Conclusions:} Our
findings suggest that morning and neutral chronotypes may be
significantly associated with a lower likelihood of depressive symptoms.
In addition, the effect of earlier chronotypes in men on depressive
symptoms in women warrants relevant clinical attention when considering
treatment.%
\end{abstract}%



\sloppy


\textbf{Introduction}

Infertility is a reproductive system disease that is characterized by
the inability to achieve a clinical pregnancy after 12 or more months of
regular unprotected sexual intercourse \textsuperscript{1}. According to
epidemiological surveys, the incidence of infertility is rising and
trending younger, affecting 186 million couples
worldwide\textsuperscript{2}, accounting for about 10\%-15\%
\textsuperscript{3}, with a prevalence of 25\% among couples of
reproductive age in China\textsuperscript{4}, which has become the third
most serious disease affecting human health after cardiovascular
diseases and tumors\textsuperscript{5}. With the implementation of
China's fertility policy, infertile individuals and couples are under
pressure from society, family, and the treatment process due to the
long-term inability to have children normally, causing great
psychological burden and social-emotional distress, which largely
affects the physical and mental health of infertility patients
\textsuperscript{6, 7}.

Depression, one of the most prevalent mental disorders, is manifested by
persistent low mood, affects 4.4\% of the global population
proportionally, or approximately 322 million people \textsuperscript{8},
and is the second leading cause of disability
worldwide\textsuperscript{9}. Currently, it is well documented that
depression is closely associated with an increased risk of developing
multiple metabolic syndromes \textsuperscript{10}, including
obesity\textsuperscript{11}, hypertension \textsuperscript{12}, and
immuno-metabolic dysregulation \textsuperscript{13}, resulting in
long-term adverse health outcomes. However, regarding the comorbidity
phenomenon of depression and infertility, it is unclear whether this
simply reflects shared risk factors. There is speculation that
depression may be a cause of infertility, its consequence, or
both\textsuperscript{14}. A previous study reported a significant
association between depression and treatment outcomes in assisted
reproductive technology (ART) \textsuperscript{15}. As a matter of fact,
depression may be even more prevalent in infertile patients compared to
the general population of reproductive age \textsuperscript{14},
considering the long course of infertility, complex etiology, many
cooperating factors, high treatment costs, cumbersome treatment process,
and the influence of social culture and traditional beliefs. There is
growing evidence that depression may be associated with multiple
factors, not only risk factors from social aspects but also
individual-level lifestyle factors, such as circadian rhythm
disturbances, which may play a significant role in the onset and
progression of depression and the overall severity of depressive
symptoms \textsuperscript{16}.

Accumulating evidence suggests that circadian rhythm disturbances are
associated with a number of adverse health outcomes\textsuperscript{17},
including but not limited to obesity\textsuperscript{18}, type 2
diabetes \textsuperscript{19}, cardiovascular diseases
\textsuperscript{20}, reproductive functions\textsuperscript{21},
psychiatric disorders \textsuperscript{22}, and cancer
\textsuperscript{23}. The chronotype is generally considered to be one
of the manifestations of circadian rhythms, and it represents the
behavioral pattern of organizing events during the 24 hours of a day,
especially referring to the subjective preference of individuals for
sleep-wake times \textsuperscript{24, 25}, which can be divided into
morning chronotype, neutral chronotype, and evening
chronotype\textsuperscript{26}. In previous studies, it was agreed that
evening chronotype was a risk factor for mental health and that
individuals with morning chronotype were at lower risk of developing
emotional problems such as anxiety and depression compared to evening
chronotype\textsuperscript{27}. With the increasing prevalence of
infertility, more and more researchers are also focusing on circadian
rhythm variations in infertile individuals and have found that worse
sleep quality and evening chronotype are more common in infertile
populations compared to those with fertility \textsuperscript{28}.
However, it is noteworthy that two prospective studies exploring the
onset and progression of infertility from a chronotype perspective
suggest suggested that morning chronotype may be a risk factor for
fertility\textsuperscript{29, 30}.

To be sure, it is necessary to examine the impact of morning chronotype
on depression during infertility treatment. Since infertility is a more
specific reproductive disorder, although not fatal, it can have a
negative impact on the individual and the spouse, or even the entire
family. Depressive symptoms, a major type of depression, without timely
intervention are likely to develop into depression. Therefore, exploring
the causes of depression is essential to promote health and function
throughout the life course. To the best of our knowledge, there is a
lack of clarity about the relationships between chronotype and
depressive symptoms during infertility treatment. Accordingly, the
objectives of this study were (1) to examine the effect of sleep type on
the depressive symptoms in subjects undergoing infertility treatment.
and (2) to assess the partner effect of spouses' chronotype on each
other's depressive symptoms.

\textbf{Materials and methods}

\textbf{Participants}

From August to October 2022, we conducted this cross-sectional study
among infertile couples in an artificial endometrial preparation from
the Center for Reproductive Medicine, First Affiliated Hospital of Anhui
Medical University (Hefei, Anhui, China). Those patients who met the
diagnostic criteria for infertility and were actively seeking treatment
were included. Subjects with a history of psychiatric disease, no embryo
transfer, comorbidities such as hypertension, diabetes, or kidney
disease, or voluntarily withdrew were excluded (n = 152). In this study,
baseline data were collected on the day of the ovulation injection
through a questionnaire that the subjects scanned a QR code using a
mobile application to access the questionnaire and completed it under
the constant supervision of highly trained research staff. The content
of the questionnaire included general demographic characteristics (age,
sex, ethnicity, education level, income, occupation, and marital
status), behavioral lifestyle (smoking or passive smoking, alcohol and
coffee consumption, Sleep, psychological state, physical activity, and
dietary habits), family and social relationships (social capital, family
power and reproductive quality of life) and fertility treatment history
(parity, gravidity, history of preterm birth and abortion, infertility
treatment timing and causes). Ultimately, after subjects with missing
data were excluded (n = 44), a total of 1,022 infertile patients were
included in the final analysis. The study protocol was approved by the
Ethics Committee of Anhui Medical University (No. 20200961) in
accordance with the guidelines of the Declaration of Helsinki and
international ethical standards. All invited participants have obtained
a written informed consent form to participate in the study
(\textbf{Figure S1} ).

\textbf{Chronotype assessment}

At present, the most widely used circadian rhythm scale is the Morning
and Evening Questionnaire, of which the Morning and Evening
Questionnaire-19 Items (MEQ-19) was first proposed by Horne and Ostberg
\textsuperscript{31}. In order to quickly screen the chronotypes, we
used the Morning and Evening Questionnaire-5 Items (MEQ-5), which was
extracted from the MEQ-19 by Adan and Almiralli through statistical
modeling \textsuperscript{32}. It is proved to have promising
psychometric properties, reliability and validity, where the Cronbach's
alpha coefficient for our study was 0.703. Due to the limited number of
individuals within the lowest or highest chronotype score group, the
chronotype of subjects were divided into evening chronotype (4-11
score), neutral chronotype (12-17 score), and morning chronotype (18-25
score) in current study based on the MEQ-5 score.

\textbf{Depressive symptoms assessment}

The participants were also asked to report their psychological status
over the past week through the Patient Health Questionnaire-9 (PHQ-9).
It is a simple and effective self-rating scale for the depressive
disorder based on the diagnostic criteria of the American Psychological
Association \textsuperscript{33}, which has been demonstrated to have
good reliability and validity by previous studies \textsuperscript{34},
with Cronbach's alpha coefficient being 0.910 in the present study. It
contains 9 items with an overall score ranging from 0 to 27, higher
scores indicate more severe depressive symptoms. In the present study,
the total score was divided into a dichotomous variable, score >4
points indicate mild and above depressive symptoms, and conversely no
depressive symptoms.

\textbf{Covariates}

All covariates were derived from self-reported baseline questionnaires.
We searched the previously relevant literature and used a directed
acyclic graph to select potential
confounders\textsuperscript{35}(\textbf{Figure S2} ). Specifically, the
following covariables are considered in the analysis: age ([?]29, 30-34,
and [?]35 years), sex (male, female), annual income (\textless{}30,000,
30,000\textasciitilde{}60,000, [?]60,000), education (middle school or
below, high/ vocational school, college degree or above), passive
smoking (never, occasionally, frequently), physical activity (low,
moderate, vigorous), living children (yes or no), infertility treatment
time ([?]6, 7\textasciitilde{}12, 13\textasciitilde{}24, \textgreater{}24
month), cause of infertility (male, female, both, and unexplained),
frequency of insomnia (never, occasionally or [?]3 per month, [?]4 per
month), nocturnal wake frequency (never, occasionally, [?]1 per night),
daytime napping (never, \textless{}1 and [?]1h ), social jetlag
(\textless{}1 and [?]1h), and nighttime sleep duration (\textless{}8 and
[?]8h).

\textbf{Statistical analysis}

Continuous variables were expressed as mean \selectlanguage{ngerman}± standard deviation (SD) or
median (P25, P75), and categorical variables were expressed as
percentages. We compared the distribution of participants with different
demographic characteristics by chronotypes (morning chronotype, neutral
chronotype, and evening chronotype) using t-tests and analysis of
variance (ANOVA) for continuous variables or Chi-square tests and
Fisher's exact test for categorical variables. Binary logistic
regression models were used to examine the relationship between
chronotype and depressive symptoms during infertility treatment.
Hypothesis testing was performed to ensure that the assumptions of the
regression model were met. Since the missing values are few, we handle
it by deleting the rows.

We used the evening chronotype as the reference group in the binary
logistic regression models~to assess the odds ratios (ORs) and 95\%
confidence intervals (CIs) for chronotype on the depressive status and
adjusted for possible confounding variables in the final model,
including age, sex, annual income, education, passive smoking, physical
activity, living children, infertility treatment time, cause of
infertility, frequency of insomnia, nocturnal wake frequency, daytime
napping, social jetlag, and nighttime sleep duration. Trend tests were
performed using the median of the different categories of chronotypes
scores as a continuous variable. Restrictive cubic splines with five
knots were conducted to characterize the dose-response curve between
sleep and depressive symptoms. We also tested the interaction effect and
estimated the relationship between chronotype and odds of depressive
symptoms by stratification of the covariates above. A sensitivity
analysis was applied to test the robustness of the results. As well, we
utilized the Actor- Partner Interdependence Mode (APIM) approach to
explore the partner effect of own chronotype on the spouse's depressive
symptoms, as recommended by Kenny et al \textsuperscript{36}. In our
study, the actor effect refers to the influence of a person's chronotype
on his/her own depressive symptoms, and the partner effect refers to the
influence of a person's chronotype on his/her spouse's depressive
symptoms. The APIM framework for a husband-wife dyad is also described
in \textbf{Figure S3} .

All the above statistical analyses were carried out using R software
version 4.1.0 (University of Auckland, Auckland, New Zealand), SPSS
version 23.0 (SPSS, Chicago, IL, USA), and Mplus software (version 8.3).
In current study, all statistical tests were double-tailed and the level
of significance was \emph{p} -value \textless{}0.05 which was considered
statistically significant.

\textbf{Results}

\textbf{General Characteristics of Participants across chronotype}

The characteristics of the 1022 (96.2\%) subjects included in present
study are shown in \textbf{Table 1} . Overall, participants included a
total of 608 females (59.5\%) and 514 males (40.5\%), with 44.7\% (n =
457) of individuals aged 30 to 34 years. According to the MEQ scores,
approximately 9.39\% of the participants were identified as evening
chronotype, while 68.2\% were neutral chronotype and 29.06\% were
morning chronotype. Significant differences were found for age, passive
smoking, education, annual income, frequency of insomnia, daytime
napping, and living children compared to these three groups (all p
\textless{}0.05). Specifically, participants in the evening chronotype
were more likely to be younger, to be free of passive smoking, had a
high or vocational school education level, a higher annual income, more
frequent insomnia, never daytime napping, lower level of physical
activity as well longer sleep and social jetlag times and shorter
infertility treatment times. In addition, we observed that 527
individuals reported mild and above depressive symptoms, representing
51.6\% of the total subjects, with a trend toward a decrease in
depressive symptoms as the chronotype from evening to neutral and then
to morning. The characteristics of participants according to depressive
phenotype are shown in \textbf{Table S1} .

\textbf{Binary logistic regression models}

We assessed the association of chronotype with the risk of depressive
status during infertility treatment, as shown in\textbf{Table 2} .
Compared to subjects in the evening chronotype group, neutral chronotype
(OR = 0.45, 95\% CI: 0.28-0.72, P trend \textless{}0.001) and morning
chronotype (OR = 0.29, 95\% CI: 0.18-0.49, P trend \textless{}0.001)
were significantly associated with lower odds of depressive symptoms.
Similarly, after adjusting for confounders, neutral chronotype (OR =
0.47, 95\% CI: 0.28-0.77, P trend \textless{}0.001) and morning
chronotype (OR = 0.32, 95\% CI: 0.18-0.57, P trend \textless{}0.001)
types were still associated with lower odds of depressive status,
although this risk reduction was attenuated. For each standard deviation
increase in MEQ-5 scores, the adjusted ORs (95\% CIs) were 0.69
(0.59-0.79, P \textless{}0.001) for depressive symptoms.

\textbf{Test for nonlinear association between MEQ-5 scores and
Depressive symptoms}

In addition, we examined the non-linear dose-response relationship
between chronotype (MEQ-5 score) and risk of depressive symptoms by
restrictive cubic splines, as shown in Figure 2. After adjusting for
age, sex, annual income, education, passive smoking, physical activity,
living children, infertility treatment time, cause of infertility,
frequency of insomnia, nocturnal wake frequency, daytime napping, social
jetlag, and nighttime sleep duration, we found that the odds of
depressive symptoms appeared to decrease with increasing MEQ-5 scores
(\emph{P} overall \textless{} 0.001); however, no nonlinear trend was
observed (\emph{P} non-linear = 0.526) (\textbf{Figure 1} ).

\textbf{Stratified and sensitivity analyses}

In stratified analysis, we did not find any differential association of
chronotype with odds of depressive symptoms, according to age, sex,
annual income, education, passive smoking, physical activity, living
children, infertility treatment time, cause of infertility, frequency of
insomnia, nocturnal wake frequency, daytime napping, social jetlag, and
nighttime sleep duration (all~\emph{p} ~for interaction \textgreater{}
0.05). As illustrated in \textbf{Figure 2} .

In addition, we performed repeated analyses to test the robustness of
the results by excluding individuals who worked shift or night, the
association of morning and neutral chronotypes with the risk of
depressive status were similar to the main analysis (OR = 0.51, 95\% CI:
0.30-0.87, \emph{P} trend \textless{}0.001; OR = 0.32, 95\% CI:
0.18-0.58, \emph{P} trend \textless{}0.001, respectively). As
illustrated in \textbf{Table S2} .

\textbf{APIM analysis}

We screened 397 infertile couples among 1022 subjects for inclusion in
the APIM with distinguishable dyads. The results showed that both female
and male chronotype exerted an actor effect on their own depressive
symptoms (\selectlanguage{greek}β\selectlanguage{english} \selectlanguage{english}= -0.514, \emph{p}  \textless{}0.001; \selectlanguage{greek}β\selectlanguage{english} \selectlanguage{english}= -0.228,\emph{p}
 \textless{}0.045, respectively). However, contrary to our expectations,
our study did not observe a strong partner effect of female/male
chronotype on spouse depressive symptoms. Specifically, the earlier
chronotype for husband had a detrimental effect on wife's depressive
symptoms (\selectlanguage{greek}β\selectlanguage{english} \selectlanguage{english}= 0.145, \emph{p}  = 0.200), yet the earlier chronotype for
the wife had a protective effect on husband's depressive symptoms
(\selectlanguage{greek}β\selectlanguage{english} \selectlanguage{english}= -0.074, \emph{p}  = 0.577), but neither was statistically
significant (\textbf{Table 3} ).

\textbf{Discussion}

Main findings

In this cross-sectional study of 1022 Chinese infertility patients, we
observed that morning and neutral chronotypes individuals were less
likely to experience depressive symptoms during assisted reproductive
treatment compared to evening chronotype, based on comparative analysis
of chronotype and PHQ-9 scores, and this protective association appeared
stronger in persons aged [?]30 years and among individuals with nighttime
sleep duration \textless{}8h or social jetlag [?]1h. As far as we know,
this is the first observational study to investigate the relationship
between chronotype and depressive status among the infertility
population who underwent assisted reproductive technology treatment.
However, findings should be interpreted cautiously as the chronotype
were based on self-reported MEQ-5 scores that may be misclassified.

Strengths and limitations

Several strengths of the current study in regard to the methods and
design, including selected infertile couples with more fully displayed
psychological characteristics as research objects, which ensured the
credibility of the research results to a certain extent. Additionally,
in terms of exposure assessment, we systematically collected sleep
characteristics through the 22-item Sleep Factor Questionnaire
(SFQ)\textsuperscript{37}. Meantime, we also adjusted for other sleep
factors that may influence the outcome for incident depression in the
analysis. We were also the first group to explore the relationships
between chronotype and depressive symptoms in infertile couple, although
no partner interdependence effects may not be found in the
relationships.

Whereas, some limitations to the present study should be noted. First,
since our design was cross-sectional studies rather than longitudinal
studies or randomized clinical trials, which may describe associations,
but are limited to causal inference. However, this study can still
provide clues about risk factors for depressive symptoms and may provide
the scientific basis for future studies. Second, participants'
chronotype and depressive symptoms were self-reported on the day of
oocyte retrieval based on validated scales with good reliability and
validity, which still may lead to bias and reduce the power of our
evidence in some respects. Third, the study was based on couples
undergoing infertility treatment, and the findings may not be directly
generalizable to other populations. Also, the data on sleep
characteristics in this study was based on the past six months, which
may not reflect long-term sleep habits. Also, this study lacks objective
indicators to explain the biological mechanism behind the relationship
between chronotype and depressive symptoms in infertile couples, future
studies need to be further verified.

Interpretation

Previous studies of chronotype and depression in infertility patients
were quite limited, First, most studies agree that chronotype may be
significantly associated with negative affect, including the general
population, the elderly, pregnant women, children, or adolescents, which
is consistent with our findings in the infertility population. Similar
findings were observed in a Mendelian randomization study, where earlier
diurnal preference was shown to be associated with a 23\% lower risk of
major depressive disorder \textsuperscript{38}. Secondly, an animal
study of cortisol-induced depression-like behavior, suggested that
circadian rhythms may cause or predict episodes of
depression\textsuperscript{39}. However, a recently conducted
longitudinal study showed that chronotype did not predict the duration
of depression or anxiety disorders \textsuperscript{40}. The above
differences may be due to the study subjects, whether the findings from
animal experiments are directly analogous to humans, as well as how well
chronotype predict the course of depressive illness, further clinical
trials or cohort studies are still needed to investigate these aspects
of health effects. Thirdly, Chronotype not only to be associated with a
depressive disorder diagnosis but also with the severity of the
disorder\textsuperscript{40}. Interestingly, a 7-year follow-up study
showed that changes in chronotype was only associated with the severity
of depressive symptoms but not with anxiety symptoms
\textsuperscript{41}. Next, the independent role of chronotype has also
been reported. A study found that daytime sleepiness and sleep debt
mediated the effects of evening chronotype preferences in young adult
college students increasing the risk of depression and anxiety, but not
in the general population of young adults \textsuperscript{42}.
Moreover, studies have confirmed that evening chronotype have a higher
risk of depression than other chronotypes and that the association
exists independently of perceived stress, poor sleep, and insufficient
sleep duration\textsuperscript{43, 44}. Undoubtedly, the findings of
these studies reinforce the importance of studying the role of
chronotype in depression. Additionally, chronotype studies in
infertility populations have shown that morning chronotype may be the
risk factor for IVF-ET outcomes, with the lowest rates of clinical
pregnancy and live birth and the highest rate of miscarriage
\textsuperscript{30}. Another prospective study also showed that
mid-sleep time (MST) earlier than 2:21 a.m. (\textless{}2:21 a.m.) or
later than 3:00 a.m. ([?]3:00 a.m.) was negatively associated with
fertilization rates \textsuperscript{29}. The effect of chronotype on
health varies across studies with different outcome variables observed.
Although morning chronotype was shown to be a protective factor for
depressive symptoms in our study, it may also be a risk factor for
physical health, more studies with larger sample sizes are necessary to
determine the effect of time type on the infertility population.

Our results confirm and extend previous epidemiological studies showing
the sex-specific effects of chronotype on depressive status. A study
among 5,550 non-shift working adults in Korea found that late chronotype
was associated with a 2.9-fold increased risk of depression in women,
but not in men \textsuperscript{45}. Our findings are broadly consistent
with previous studies and extend these observations further into the
infertility population. Specifically, we found through APIM that own
depressive symptoms may not be influenced by the chronotype of the
partner. Notably, our findings also showed a significant interaction
between age and chronotype on the odds of developing depressive
symptoms, whereby the health benefits of depressive symptoms were
greater for morning chronotype and neutral chronotype in participants
aged [?]30 years. The chronotype depend on genetic and age-related
factors, and it becomes earlier as aging progresses\textsuperscript{46},
generally adolescents and young adults show the evening chronotype
\textsuperscript{47}. A study with a predominantly rural population
reported that mild to severe depression was significantly associated
with later chronotype and higher social jetlag (\textgreater{} 2h),
especially in ages 31-40 years\textsuperscript{48}, which is broadly
consistent with our study. In addition, we observed that sleep
deprivation and high social jetlag may be another cause of depressive
symptoms, morning chronotype and neutral chronotype produced stronger
health benefits for depressive symptoms in subjects with high social
jetlag ([?]1h) and sleep deprivation (\textless{}8h). A large number of
epidemiological studies have explored the relationship between sleep
deprivation and depression, showing sleep deprivation to be an important
risk factor for the development of depression and this association may
be driven by the pathway of sleep disorder. Also, one recent study has
shown that social jetlag is significantly associated with depression and
independent of sleep debt\textsuperscript{49}. It is partially
consistent with our conjecture, but further clinical trials or cohort
studies are needed to validate these health effects in the future.

Although the underlying mechanisms on the association between chronotype
and depressive symptoms are poorly understood, there are possible
mechanisms. First, it has been well-documented that the amygdala
reactivity plays a crucial role in emotional
outcomes\textsuperscript{50}. Specifically, the later chronotype was
associated with increased reactivity of the amygdala to negative
affective stimuli, and similar findings have been reported in patients
with depression and in high-risk populations, including highly neurotic
and with family history of depression \textsuperscript{51}. Secondly,
apart from the degree of amygdala activation related to emotional
processing, there are also differences in the functional connectivity of
the amygdala and dorsal anterior cingulate cortex. Horne and colleagues
found significantly reduced functional connectivity between amygdala and
dorsal anterior cingulate cortex in the later
chronotype\textsuperscript{51}. It means that the evening chronotype may
produce a stronger emotional response to negative stimuli, which
inhibits the dorsal anterior cingulate regulation to the amygdala and
thus affects emotion modulation.

\textbf{Conclusions}

To conclude, our study found that significantly associated between
chronotype and depressive symptoms in infertility patients, although
there may not be a partner effect. Morning and neutral chronotypes may
be effective in alleviating depressive symptoms during infertility
treatment. From a clinical and public health perspective, improving the
psychological status of infertility patients during treatment may
benefit reproductive treatment outcomes. Also, the underlying causes of
depressive symptoms may be multifactorial, and additional prospective
studies are needed to validate this association as well as to identify
effective strategies to promote mental health in this population.

\textbf{Footnote}

\textbf{Author' contributions:} Fei Jiang had full access to all the
data in the study and take responsibility for the integrity of the data
and the accuracy of the data analysis. Study concept and design: Danni
Wang. Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Fei Jiang and Danni Wang. Critical revision
of the manuscript for important intellectual content: All authors.
Statistical analysis: Fei Jiang. Obtained funding: Danni Wang.
Administrative, technical, or material support: Danni Wang. Study
supervision: Danni Wang.

\textbf{Acknowledgments:} The authors would like to thank the Center for
Reproductive Medicine, First Affiliated Hospital of Anhui Medical
University for their technical support for data collection. The authors
would also like to thank the study participants and staff.

\textbf{Institutional Review Board Statement:} The Ethics Committee of
Anhui Medical University approved the study protocols (No. 20200961).
And the study design was confirmed in accordance with the Helsinki
Declaration.

\textbf{Informed Consent Statement:} All participants provided informed
consent before enrollment.

\textbf{Funding:} This work was supported by the National Natural
Science Foundation of China (72004001), and grants from Anhui Provincial
Scientific Research and Humanities Project of Colleges and Universities
(2022AH050627).

\textbf{Disclosure statement:} All authors have completed the ICMJE
uniform disclosure form and have no conflicts of interest to declare.

\textbf{Attestation statement:} The subjects in this trial have not
concomitantly been involved in other randomized trials. Data regarding
any of the subjects in the study has not been previously published
unless specified. Data will be made available to the editors of the
journal for review or query upon request.

\textbf{Data sharing statement:} Data will be made available on request.

\textbf{Word counting:} 222 words for abstract and 3784 words for text.

\textbf{Number of figures and tables} : 3 tables, 2 figures, 2
supplemental tables, and 3 supplemental figures.

\textbf{References}

1. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de Mouzon J,
Sokol R, et al. The International Glossary on Infertility and Fertility
Care, 2017. Hum Reprod. 2017 Sep 1;32(9):1786-801.

2. Inhorn MC, Patrizio P. Infertility around the globe: new thinking on
gender, reproductive technologies and global movements in the 21st
century. Hum Reprod Update. 2015 Jul-Aug;21(4):411-26.

3. Tamrakar SR, Bastakoti R. Determinants of Infertility in Couples. J
Nepal Health Res Counc. 2019 Apr 28;17(1):85-9.

4. Zhou Z, Zheng D, Wu H, Li R, Xu S, Kang Y, et al. Epidemiology of
infertility in China: a population-based study. BJOG. 2018
Mar;125(4):432-41.

5. Agarwal A, Majzoub A, Parekh N, Henkel R. A Schematic Overview of the
Current Status of Male Infertility Practice. World J Mens Health. 2020
Jul;38(3):308-22.

6. Cocchiaro T, Meneghini C, Dal Lago A, Fabiani C, Amodei M, Miriello
D, et al. Assessment of sexual and emotional distress in infertile
couple: validation of a new specific psychometric tool. J Endocrinol
Invest. 2020 Dec;43(12):1729-37.

7. Kamboj N, Saraswathy KN, Prasad S, Babu N, Puri M, Sharma A, et al.
Women infertility and common mental disorders: A cross-sectional study
from North India. PLoS One. 2023;18(1):e0280054.

8. Friedrich MJ. Depression Is the Leading Cause of Disability Around
the World. JAMA. 2017 Apr 18;317(15):1517.

9. Refisch A, Sen ZD, Klassert TE, Busch A, Besteher B, Danyeli LV, et
al. Microbiome and immuno-metabolic dysregulation in patients with major
depressive disorder with atypical clinical presentation.
Neuropharmacology. 2023 Sep 1;235:109568.

10. Ferriani LO, Silva DA, Molina M, Mill JG, Brunoni AR, da Fonseca
MJM, et al. Depression is a risk factor for metabolic syndrome: Results
from the ELSA-Brasil cohort study. J Psychiatr Res. 2023 Feb;158:56-62.

11. Ramzi NH, Auvinen J, Veijola J, Miettunen J, Ala-Mursula L, Sebert
S, et al. Depression mediates the relationship between alexithymia and
obesity in the Northern Finland Birth Cohort 1966 (NFBC1966). J Affect
Disord. 2023 Jun 15;331:1-7.

12. Shah RM, Doshi S, Shah S, Patel S, Li A, Diamond JA. Impacts of
Anxiety and Depression on Clinical Hypertension in Low-Income US Adults.
High Blood Press Cardiovasc Prev. 2023 Jun 1:1-6.

13. Toenders YJ, Schmaal L, Nawijn L, Han LKM, Binnewies J, van der Wee
NJA, et al. The association between clinical and biological
characteristics of depression and structural brain alterations. J Affect
Disord. 2022 Sep 1;312:268-74.

14. Vo TM, Tran QT, Le CV, Do TT, Le TM. Depression and associated
factors among infertile women at Tu Du hospital, Vietnam: a
cross-sectional study. International journal of women's health.
2019;11:343-51.

15. Purewal S, Chapman SCE, van den Akker OBA. Depression and state
anxiety scores during assisted reproductive treatment are associated
with outcome: a meta-analysis. Reprod Biomed Online. 2018
Jun;36(6):646-57.

16. Monteggia LM, Kavalali ET. Circadian rhythms: Depression brought to
light. Nature. 2012 Nov 22;491(7425):537-8.

17. Comas M, Solis Flores A, Lovato N, Miller CB, Bartlett DJ, Grunstein
RR, et al. The Relationship between Anxiety, Subjective and Objective
Sleep, Chronotype and Circadian Rhythms with Depressive Symptoms in
Insomnia Disorder. Brain Sci. 2023 Apr 4;13(4).

18. Li Y, Ma J, Yao K, Su W, Tan B, Wu X, et al. Circadian rhythms and
obesity: Timekeeping governs lipid metabolism. J Pineal Res. 2020
Oct;69(3):e12682.

19. Peng X, Fan R, Xie L, Shi X, Dong K, Zhang S, et al. A Growing Link
between Circadian Rhythms, Type 2 Diabetes Mellitus and Alzheimer's
Disease. Int J Mol Sci. 2022 Jan 3;23(1).

20. Mentzelou M, Papadopoulou SK, Papandreou D, Spanoudaki M, Dakanalis
A, Vasios GK, et al. Evaluating the Relationship between Circadian
Rhythms and Sleep, Metabolic and Cardiovascular Disorders: Current
Clinical Evidence in Human Studies. Metabolites. 2023 Mar 1;13(3).

21. Caetano G, Bozinovic I, Dupont C, L\selectlanguage{ngerman}éger D, Lévy R, Sermondade N.
Impact of sleep on female and male reproductive functions: a systematic
review. Fertility and sterility. 2021 Mar;115(3):715-31.

22. Codoner-Franch P, Gombert M, Martinez-Raga J, Cenit MC. Circadian
Disruption and Mental Health: The Chronotherapeutic Potential of
Microbiome-Based and Dietary Strategies. Int J Mol Sci. 2023 Apr
20;24(8).

23. Lotti S, Dinu M, Colombini B, Amedei A, Sofi F. Circadian rhythms,
gut microbiota, and diet: Possible implications for health. Nutr Metab
Cardiovasc Dis. 2023 May 14.

24. Roenneberg T, Kuehnle T, Juda M, Kantermann T, Allebrandt K, Gordijn
M, et al. Epidemiology of the human circadian clock. Sleep Med Rev. 2007
Dec;11(6):429-38.

25. Senesi P, Ferrulli A, Luzi L, Terruzzi I. Chrono-communication and
cardiometabolic health: The intrinsic relationship and therapeutic
nutritional promises. Frontiers in endocrinology. 2022;13:975509.

26. Park H, Lee HK, Lee K. Chronotype and suicide: The mediating effect
of depressive symptoms. Psychiatry Res. 2018 Nov;269:316-20.

27. Antypa N, Vogelzangs N, Meesters Y, Schoevers R, Penninx BW.
Chronotype Associations with Depression and Anxiety Disorders in a Large
Cohort Study. Depress Anxiety. 2016 Jan;33(1):75-83.

28. Ozcelik C, Varli B, Gokce A, Takmaz T, Cetin C, Ozcan P. Evaluation
of chronotype and sleep quality in infertile population and comparison
with fertile population: a cross-sectional study. J Psychosom Obstet
Gynaecol. 2023 Dec;44(1):2148523.

29. Yao QY, Yuan XQ, Liu C, Du YY, Yao YC, Wu LJ, et al. Associations of
sleep characteristics with outcomes of IVF/ICSI treatment: a prospective
cohort study. Hum Reprod. 2022 May 30;37(6):1297-310.

30. Liu Z, Zheng Y, Wang B, Li J, Qin L, Li X, et al. The impact of
sleep on in~vitro fertilization embryo transfer outcomes: a prospective
study. Fertility and sterility. 2023 Jan;119(1):47-55.

31. Horne JA, Ostberg O. A self-assessment questionnaire to determine
morningness-eveningness in human circadian rhythms. Int J Chronobiol.
1976;4(2):97-110.

32. Adan A, Almirall H. The influence of age, work schedule and
personality on morningness dimension. Int J Psychophysiol. 1992
Mar;12(2):95-9.

33. Kroenke K. PHQ-9: global uptake of a depression scale. World
Psychiatry. 2021 Feb;20(1):135-6.

34. Yin L, Teklu S, Pham H, Li R, Tahir P, Garcia ME. Validity of the
Chinese Language Patient Health Questionnaire 2 and 9: A Systematic
Review. Health Equity. 2022;6(1):574-94.

35. Textor J, van der Zander B, Gilthorpe MS, Liskiewicz M, Ellison GT.
Robust causal inference using directed acyclic graphs: the R package
'dagitty'. International journal of epidemiology. 2016 Dec
1;45(6):1887-94.

36. Kenny DA, Kashy DA, Cook WL. Dyadic data analysis. 2006 {[}cited;
Available from:

37. Yang WS, Wang X, Deng Q, Zhao H, Fan WY. Sleep duration and breast
cancer risk in the breast cancer detection demonstration project
follow-up cohort: true associations or bias? British journal of cancer.
2015 May 26;112(11):1838-9.

38. Daghlas I, Lane JM, Saxena R, Vetter C. Genetically Proxied Diurnal
Preference, Sleep Timing, and Risk of Major Depressive Disorder. JAMA
psychiatry. 2021 Aug 1;78(8):903-10.

39. Spulber S, Conti M, DuPont C, Raciti M, Bose R, Onishchenko N, et
al. Alterations in circadian entrainment precede the onset of
depression-like behavior that does not respond to fluoxetine.
Translational psychiatry. 2015 Jul 14;5(7):e603.

40. Druiven SJM, Knapen SE, Penninx B, Antypa N, Schoevers RA, Riese H,
et al. Can chronotype function as predictor of a persistent course of
depressive and anxiety disorder? J Affect Disord. 2019 Jan 1;242:159-64.

41. Druiven SJM, Hovenkamp-Hermelink JHM, Knapen SE, Kamphuis J, Haarman
BCM, Penninx B, et al. Stability of chronotype over a 7-year follow-up
period and its association with severity of depressive and anxiety
symptoms. Depress Anxiety. 2020 May;37(5):466-74.

42. Dickinson DL, Wolkow AP, Rajaratnam SMW, Drummond SPA. Personal
sleep debt and daytime sleepiness mediate the relationship between sleep
and mental health outcomes in young adults. Depress Anxiety. 2018
Aug;35(8):775-83.

43. Tonon AC, Carissimi A, Schimitt RL, de Lima LS, Pereira FDS, Hidalgo
MP. How do stress, sleep quality, and chronotype associate with
clinically significant depressive symptoms? A study of young male
military recruits in compulsory service. Revista brasileira de
psiquiatria (Sao Paulo, Brazil : 1999). 2020 Jan-Feb;42(1):54-62.

44. Merikanto I, Kronholm E, Peltonen M, Laatikainen T, Vartiainen E,
Partonen T. Circadian preference links to depression in general adult
population. J Affect Disord. 2015 Dec 1;188:143-8.

45. Kim KM, Han SM, Heo K, Kim WJ, Chu MK. Sex differences in the
association between chronotype and risk of depression. Scientific
reports. 2020 Oct 28;10(1):18512.

46. Taillard J, Sagaspe P, Philip P, Bioulac S. Sleep timing, chronotype
and social jetlag: Impact on cognitive abilities and psychiatric
disorders. Biochemical pharmacology. 2021 Sep;191:114438.

47. Keller LK, Zöschg S, Grünewald B, Roenneberg T, Schulte-Körne G.
{[}Chronotype and depression in adolescents -- a review{]}. Zeitschrift
fur Kinder- und Jugendpsychiatrie und Psychotherapie. 2016;44(2):113-26.

48. Levandovski R, Dantas G, Fernandes LC, Caumo W, Torres I, Roenneberg
T, et al. Depression scores associate with chronotype and social jetlag
in a rural population. Chronobiology international. 2011
Nov;28(9):771-8.

49. Okajima I, Komada Y, Ito W, Inoue Y. Sleep Debt and Social Jetlag
Associated with Sleepiness, Mood, and Work Performance among Workers in
Japan. International journal of environmental research and public
health. 2021 Mar 12;18(6).

50. Schiel JE, Tamm S, Holub F, Petri R, Dashti HS, Domschke K, et al.
Associations Between Sleep Health and Amygdala Reactivity to Negative
Facial Expressions in the UK Biobank Cohort. Biological psychiatry. 2022
Nov 1;92(9):693-700.

51. Horne CM, Norbury R. Late chronotype is associated with enhanced
amygdala reactivity and reduced fronto-limbic functional connectivity to
fearful versus happy facial expressions. NeuroImage. 2018 May
1;171:355-63.

\textbf{Table 1.} The characteristics of participants according to
Morning and Evening Questionnaire score status \selectlanguage{english}\textsuperscript{+}.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
\begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Characteristic\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Overall\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Chronotypes\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Chronotypes\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
Chronotypes\textsuperscript{++}\strut
\end{minipage} & \begin{minipage}[b]{0.14\columnwidth}\raggedright\strut
\emph{p}\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\par\null\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Evening Chronotype\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Neutral Chronotype\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Morning Chronotype\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
No. of Participants\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
1022\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
96(9.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
697(68.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
229(22.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Age~(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.010\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]29\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
377 (36.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
41 (42.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
268 (38.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
68 (29.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30-34\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
457 (44.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
46 (47.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
305 (43.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
106 (46.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]35\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
188 (18.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9 (9.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
124 (17.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
55 (24.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Sex (Female, \%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
608 (59.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
56 (58.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
428 (61.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
124 (54.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.148\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Education (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.011\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Middle school or below\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
302 (29.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
24 (25.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
190 (27.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
88 (38.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
High/ vocational school\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
382 (37.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
43 (44.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
263 (37.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
76 (33.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
College degree or above\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
338 (33.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29 (30.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
244 (35.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
65 (28.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Annual incomes (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.043\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}30, 000\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
388 (38.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30 (31.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
255 (36.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
103 (45.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
30, 000-60, 000\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
242 (23.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (24.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
178 (25.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
41 (17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]60, 000\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
392 (38.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
43 (44.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
264 (37.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
85 (37.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Passive smoking (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
326 (31.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
49 (51.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
220 (31.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
57 (24.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Occasionally\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
591 (57.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45 (46.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
419 (60.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
127 (55.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Frequently\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
105 (10.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
2 (2.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
58 (8.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
45 (19.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Physical activity (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.467\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Low\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
342 (33.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
34 (35.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
223 (32.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
85 (37.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Moderate\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
341 (33.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31 (32.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
244 (35.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
66 (28.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Vigorous\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
339 (33.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31 (32.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
230 (33.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
78 (34.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Cause of infertility (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.923\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Male factor\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
179 (17.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14 (14.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
126 (18.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
39 (17.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Female factor\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
365 (35.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
39 (40.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
242 (34.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
84 (36.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Both\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
249 (24.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
21 (21.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
174 (25.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
54 (23.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Unexplained\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
229 (22.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22 (22.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
155 (22.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
52 (22.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Living children (yes, \%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
162 (15.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
9 (9.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
105 (15.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
48 (21.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.020\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Infertility treatment time\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.335\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]6 month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
342 (33.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
40 (41.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
223 (32.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
79 (34.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
7-12 month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
217 (21.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
17 (17.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
152 (21.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
48 (21.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13-24 month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
310 (30.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
26 (27.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
223 (32.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
61 (26.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textgreater{}24 month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
153 (15.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
13 (13.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
99 (14.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
41 (17.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Frequency of insomnia (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
236 (23.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
14 (14.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
156 (22.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
66 (28.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
Occasionally or [?]3 per month\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
687 (67.2)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
60 (62.5)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
476 (68.3)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
151 (65.9)\strut
\end{minipage} & \begin{minipage}[t]{0.16\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]4 per month\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
99 (9.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22 (22.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
65 (9.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
12 (5.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Nocturnal wake frequency (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.087\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
158 (15.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
23 (24.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
106 (15.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29 (12.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Occasionally\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
471 (46.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
42 (43.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
327 (46.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
102 (44.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]1 per night\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
393 (38.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
31 (32.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
264 (37.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
98 (42.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Daytime napping (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.004\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Never\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
295 (28.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
41 (42.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
199 (28.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
55 (24.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
525 (51.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
33 (34.4)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
366 (52.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
126 (55.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
[?]1\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
202 (19.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
22 (22.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
132 (18.9)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
48 (21.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Social jetlag ([?]1 h, \%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
211 (20.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
29 (30.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
147 (21.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
35 (15.3)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.009\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Nighttime sleep duration ([?]8 h, \%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
680 (66.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
71 (74.0)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
454 (65.1)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
155 (67.7)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
0.210\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
Depression symptoms (yes, \%)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
527 (51.6)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
68 (70.8)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
364 (52.2)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
95 (41.5)\strut
\end{minipage} & \begin{minipage}[t]{0.14\columnwidth}\raggedright\strut
\textless{}0.001\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

Note: \textsuperscript{+} Values were presented as mean \selectlanguage{ngerman}± SD or
percentages; \selectlanguage{english}\textsuperscript{++} Evening Chronotype: 4-11 score; Neutral
Chronotype: 12-17 score; Morning Chronotype: 18-25 score.

\textbf{Table 2} . Association between chronotype and depressive
symptoms in infertility populations according to Morning and Evening
Questionnaire score status \selectlanguage{english}\textsuperscript{+}.\selectlanguage{english}
\begin{longtable}[]{@{}llllll@{}}
\toprule
Depressive symptoms & OR (95\% CIs) & OR (95\% CIs) & OR (95\% CIs) &
Per 1-SD &
\emph{P}\textsubscript{trend}\textsuperscript{d}\tabularnewline
\midrule
\endhead
& Evening chronotypes & Neutral chronotype & Morning chronotype &
&\tabularnewline
No. of cases/participants & 68/96 & 364/697 & 95/229 & &\tabularnewline
Model 1\textsuperscript{a} & Reference & 0.45 (0.28-0.72)
\textsuperscript{**} & 0.29 (0.18-0.49) \textsuperscript{***} & 0.68
(0.60-0.78) \textsuperscript{***} & \textless{}0.001\tabularnewline
Model 2\textsuperscript{b} & Reference & 0.45 (0.28-0.73)
\textsuperscript{**} & 0.31 (0.18-0.53) \textsuperscript{***} & 0.68
(0.59-0.78) \textsuperscript{***} & \textless{}0.001\tabularnewline
Model 3\textsuperscript{c} & Reference & 0.47 (0.28-0.77)
\textsuperscript{**} & 0.32 (0.18-0.57) \textsuperscript{***} & 0.69
(0.59-0.79) \textsuperscript{***} & \textless{}0.001\tabularnewline
\bottomrule
\end{longtable}

Note: CIs, confidence intervals; ORs, odds ratios.

\textsuperscript{+} Evening Chronotype: 4-11 score; Neutral Chronotype:
12-17 score; Morning Chronotype: 18-25 score.

\textsuperscript{*} P \textless{}0.05, \textsuperscript{**} P
\textless{}0.01, \textsuperscript{***} P \textless{}0.001.

\textsuperscript{a} Model 1: did not adjust for the covariates.

\textsuperscript{b} Model 2: additionally included age, sex, education,
annual incomes, education, passive smoking, physical activity, cause of
infertility, living children, and infertility treatment time.

\textsuperscript{c} Model 3: additionally included frequency of
insomnia, nocturnal wake frequency, daytime napping, social jetlag, and
nighttime sleep duration.

\textsuperscript{d} The trend test was performed by assigning medians to
three categories as a continuous variable in the models.

\textbf{Table 3} . Actor and partner effects of chronotype on depressive
symptoms in infertile couples (n = 397 couples)\selectlanguage{english}
\begin{longtable}[]{@{}lllllll@{}}
\toprule
& Female & Female & Male & Male & Male &\tabularnewline
\midrule
\endhead
& \selectlanguage{greek}β \selectlanguage{english}(SE) & \emph{P} & \emph{P} & \selectlanguage{greek}β \selectlanguage{english}(SE) & \emph{P} &
\emph{P}\tabularnewline
Actor's depressive symptoms & -0.514(0.139) & 0.001 & 0.001 & -
0.228(0.114) & 0.045 & 0.045\tabularnewline
Partner's depressive symptoms & 0.145 (0.113) & 0.200 & 0.200 & -
0.074(0.132) & 0.577 & 0.577\tabularnewline
\bottomrule
\end{longtable}

Note: \selectlanguage{greek}β, \selectlanguage{english}Standardized Coefficient; SE, Standard Error

\textbf{Table Legends}

\textbf{Table 1.} The characteristics of participants according to
Morning and Evening Questionnaire score status \textsuperscript{+}.

Note: \textsuperscript{+} Values were presented as mean \selectlanguage{ngerman}± SD or
percentages; \selectlanguage{english}\textsuperscript{++} Evening Chronotype: 4-11 score; Neutral
Chronotype: 12-17 score; Morning Chronotype: 18-25 score.

\textbf{Table 2} . Association between chronotype and depressive
symptoms in infertility populations according to Morning and Evening
Questionnaire score status \selectlanguage{english}\textsuperscript{+}.

Note: CIs, confidence intervals; ORs, odds ratios.
\selectlanguage{english}\textsuperscript{+}Evening Chronotype: 4-11 score; Neutral Chronotype:
12-17 score; Morning Chronotype: 18-25 score. \selectlanguage{english}\textsuperscript{*} P
\textless{}0.05,\selectlanguage{english}\textsuperscript{**} P \textless{}0.01,
\selectlanguage{english}\textsuperscript{***} P \textless{}0.001. \textsuperscript{a} Model 1:
did not adjust for the covariates. \textsuperscript{b} Model 2:
additionally included age, sex, education, annual incomes, education,
passive smoking, physical activity, cause of infertility, living
children, and infertility treatment time. \textsuperscript{c} Model 3:
additionally included frequency of insomnia, nocturnal wake frequency,
daytime napping, social jetlag, and nighttime sleep duration.
\textsuperscript{d} The trend test was performed by assigning medians to
three categories as a continuous variable in the models.

\textbf{Table 3} . Actor and partner effects of chronotype on depressive
symptoms in infertile couples (n = 397 couples).

Note: \selectlanguage{greek}β, \selectlanguage{english}Standardized Coefficient; SE, Standard Error

\textbf{Table S1.} The characteristics of participants according to
depression phenotypes \textsuperscript{+}.

Note: \textsuperscript{+} Values were presented as mean \selectlanguage{ngerman}± SD or
percentages; \selectlanguage{english}\textsuperscript{++} non-Depression: 0-4 score; Depression:
5-27 score.

Note: CIs, confidence intervals; ORs, odds ratios.
\selectlanguage{english}\textsuperscript{+}Evening Chronotype: 4-11 score; Neutral Chronotype:
12-17 score; Morning Chronotype: 18-25 score.\selectlanguage{english}\textsuperscript{*} P
\textless{}0.05, \selectlanguage{english}\textsuperscript{**} P
\textless{}0.01,\selectlanguage{english}\textsuperscript{***} P \textless{}0.001.
\textsuperscript{a} Model 1: did not adjust for the covariates.
\textsuperscript{b} Model 2: additionally included age, sex, education,
annual incomes, education, passive smoking, physical activity, cause of
infertility, living children, and infertility treatment time.
\textsuperscript{c} Model 3: additionally included frequency of
insomnia, nocturnal wake frequency, daytime napping, social jetlag, and
nighttime sleep duration.\textsuperscript{d} The trend test was
performed by assigning medians to three categories as a continuous
variable in the models.

\textbf{Table S2} . Sensitivity analysis on association between
chronotype and depressive states among individuals without night/shifts
work in infertility populations according to Morning and Evening
Questionnaire score status \selectlanguage{english}\textsuperscript{+}.

\textbf{Figure Legends}

\textbf{Figure 1.} Visualization of the dose-response relationship
between chronotype and depressive symptoms based on restricted cubic
splines. Abbreviations: OR, Odds ratio; CI, confidence interval.
Covariates adjusted in the models were the same as those in model 4
in\textbf{Table 2} (see \textbf{Table 2} footnote).

\textbf{Figure 2.} Stratified analysis on the association between
chronotype and odds of depressive symptoms. Abbreviations: OR, Odds
ratio. Covariates adjusted in the models were the same as those in model
4 in \textbf{Table 2} (see \textbf{Table 2} footnote).

\textbf{Figure S1.} Flow chart of selection of participants in the
analysis.

\textbf{Figure S2.} Directed acyclic graph for confounder selection

\textbf{Figure S3.} Actor--Partner Interdependence Model of chronotype
and depressive symptoms in infertile couples.

Note: Am: actor effect of female's chronotype on her own depressive
symptoms; Af: actor effect of male's chronotype on his own depressive
symptoms; Pfm: partner effect of female's chronotype on male's
depressive symptoms; Pmf: partner effect of male's chronotype on
female's depressive symptoms; Em~and Ef: residual errors on depressive
symptoms for female and male, respectively.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-1/Figure-1}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-2/Figure-2}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Figure S1.docx`  available at \url{https://authorea.com/users/668419/articles/668302-association-of-chronotype-and-depressive-symptoms-in-chinese-infertile-population-undergoing-assisted-reproductive-technology}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/Figure-S2/Figure-S2}

\end{center}
\end{figure}

\textbf{Hosted file}

\verb`Figure S3.docx`  available at \url{https://authorea.com/users/668419/articles/668302-association-of-chronotype-and-depressive-symptoms-in-chinese-infertile-population-undergoing-assisted-reproductive-technology}

\textbf{Hosted file}

\verb`Table S1.docx`  available at \url{https://authorea.com/users/668419/articles/668302-association-of-chronotype-and-depressive-symptoms-in-chinese-infertile-population-undergoing-assisted-reproductive-technology}

\textbf{Hosted file}

\verb`Table S2.docx`  available at \url{https://authorea.com/users/668419/articles/668302-association-of-chronotype-and-depressive-symptoms-in-chinese-infertile-population-undergoing-assisted-reproductive-technology}

\selectlanguage{english}
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\end{document}

